{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T02:39:52Z","timestamp":1781663992649,"version":"3.54.5"},"reference-count":338,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,7,12]],"date-time":"2022-07-12T00:00:00Z","timestamp":1657584000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Age-related macular degeneration (AMD) is among the leading causes of irreversible blindness worldwide. In addition to environmental risk factors, such as tobacco use and diet, genetic background has long been established as a major risk factor for the development of AMD. However, our ability to predict disease risk and personalize treatment remains limited by our nascent understanding of the molecular mechanisms underlying AMD pathogenesis. Research into the molecular genetics of AMD over the past two decades has uncovered 52 independent gene variants and 34 independent loci that are implicated in the development of AMD, accounting for over half of the genetic risk. This research has helped delineate at least five major pathways that may be disrupted in the pathogenesis of AMD: the complement system, extracellular matrix remodeling, lipid metabolism, angiogenesis, and oxidative stress response. This review surveys our current understanding of each of these disease mechanisms, in turn, along with their associated pathogenic gene variants. Continued research into the molecular genetics of AMD holds great promise for the development of precision-targeted, personalized therapies that bring us closer to a cure for this debilitating disease.<\/jats:p>","DOI":"10.3390\/genes13071233","type":"journal-article","created":{"date-parts":[[2022,7,12]],"date-time":"2022-07-12T20:52:41Z","timestamp":1657659161000},"page":"1233","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Molecular Genetic Mechanisms in Age-Related Macular Degeneration"],"prefix":"10.3390","volume":"13","author":[{"given":"Aumer","family":"Shughoury","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Eugene and Marilyn Glick Eye Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duriye Damla","family":"Sevgi","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Eugene and Marilyn Glick Eye Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas A.","family":"Ciulla","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Eugene and Marilyn Glick Eye Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA"},{"name":"Clearside Biomedical, Inc., Alpharetta, GA 30005, USA"},{"name":"Midwest Eye Institute, Indianapolis, IN 46290, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e106","DOI":"10.1016\/S2214-109X(13)70145-1","article-title":"Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: A systematic review and meta-analysis","volume":"2","author":"Wong","year":"2014","journal-title":"Lancet Glob. Health"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1136\/bjo.85.3.327","article-title":"Utility values associated with blindness in an adult population","volume":"85","author":"Brown","year":"2001","journal-title":"Br. J. Ophthalmol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"4234","DOI":"10.1167\/iovs.12-9580","article-title":"The impact of visual and nonvisual factors on quality of life and adaptation in adults with visual impairment","volume":"53","author":"Dickinson","year":"2012","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1001\/archopht.116.4.514","article-title":"The psychosocial impact of macular degeneration","volume":"116","author":"Williams","year":"1998","journal-title":"Arch. Ophthalmol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2483","DOI":"10.2147\/OPTH.S185052","article-title":"The burden of neovascular age-related macular degeneration: A patient\u2019s perspective","volume":"12","author":"Spooner","year":"2018","journal-title":"Clin. Ophthalmol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/S0008-4182(05)80070-5","article-title":"Age-related macular degeneration: Economic burden and value-based medicine analysis","volume":"40","author":"Brown","year":"2005","journal-title":"Can. J. Ophthalmol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1001\/archophthalmol.2009.58","article-title":"Forecasting age-related macular degeneration through the year 2050: The potential impact of new treatments","volume":"127","author":"Rein","year":"2009","journal-title":"Arch. Ophthalmol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1007\/978-1-4419-5635-4_5","article-title":"Bisretinoids of RPE lipofuscin: Trigger for complement activation in age-related macular degeneration","volume":"703","author":"Sparrow","year":"2010","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1152\/physrev.00021.2004","article-title":"The retinal pigment epithelium in visual function","volume":"85","author":"Strauss","year":"2005","journal-title":"Physiol. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/S0039-6257(00)00140-5","article-title":"The role of oxidative stress in the pathogenesis of age-related macular degeneration","volume":"45","author":"Beatty","year":"2000","journal-title":"Surv. Ophthalmol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1136\/thx.2003.012468","article-title":"Acute effects of cigarette smoke on inflammation and oxidative stress: A review","volume":"59","author":"Postma","year":"2004","journal-title":"Thorax"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1038\/sj.eye.6701978","article-title":"Smoking and age-related macular degeneration: A review of association","volume":"19","author":"Thornton","year":"2005","journal-title":"Eye"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1016\/S0161-6420(00)00580-7","article-title":"Risk factors for age-related macular degeneration: Pooled findings from three continents","volume":"108","author":"Smith","year":"2001","journal-title":"Ophthalmology"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Age-Related Eye Disease Study Research Group (2000). Risk factors associated with age-related macular degeneration. A case-control study in the age-related eye disease study: Age-Related Eye Disease Study Report Number 3. Ophthalmology, 107, 2224\u20132232.","DOI":"10.1016\/S0161-6420(00)00409-7"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1016\/S0002-9394(14)70906-7","article-title":"A hemodynamic model of the pathogenesis of age-related macular degeneration","volume":"124","author":"Friedman","year":"1997","journal-title":"Am. J. Ophthalmol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"18569","DOI":"10.1073\/pnas.1115497108","article-title":"Complementing apolipoprotein secretion by cultured retinal pigment epithelium","volume":"108","author":"Curcio","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1038\/s41572-021-00265-2","article-title":"Age-related macular degeneration","volume":"7","author":"Fleckenstein","year":"2021","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1016\/j.ophtha.2019.11.004","article-title":"Consensus Nomenclature for Reporting Neovascular Age-Related Macular Degeneration Data: Consensus on Neovascular Age-Related Macular Degeneration Nomenclature Study Group","volume":"127","author":"Spaide","year":"2020","journal-title":"Ophthalmology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2204","DOI":"10.1097\/IAE.0000000000000867","article-title":"Detection of Nonexudative Choroidal Neovascularization in Age-Related Macular Degeneration with Optical Coherence Tomography Angiography","volume":"35","author":"Palejwala","year":"2015","journal-title":"Retina"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/j.ajo.2011.02.025","article-title":"Risk factors for four-year incidence and progression of age-related macular degeneration: The los angeles latino eye study","volume":"152","author":"Choudhury","year":"2011","journal-title":"Am. J. Ophthalmol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1001\/jama.1996.03540140029022","article-title":"A prospective study of cigarette smoking and age-related macular degeneration in women","volume":"276","author":"Seddon","year":"1996","journal-title":"JAMA"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1001\/jama.1996.03540140035023","article-title":"A prospective study of cigarette smoking and risk of age-related macular degeneration in men","volume":"276","author":"Christen","year":"1996","journal-title":"JAMA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1016\/j.ophtha.2006.09.022","article-title":"Cigarette smoking and age-related macular degeneration in the EUREYE Study","volume":"114","author":"Chakravarthy","year":"2007","journal-title":"Ophthalmology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1001\/archopht.119.8.1191","article-title":"Dietary fat and risk for advanced age-related macular degeneration","volume":"119","author":"Seddon","year":"2001","journal-title":"Arch. Ophthalmol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3101","DOI":"10.1001\/jama.294.24.3101","article-title":"Dietary intake of antioxidants and risk of age-related macular degeneration","volume":"294","author":"Boekhoorn","year":"2005","journal-title":"JAMA"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1093\/oxfordjournals.aje.a113629","article-title":"Senile macular degeneration: A case-control study","volume":"118","author":"Hyman","year":"1983","journal-title":"Am. J. Epidemiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/S1350-9462(98)00025-1","article-title":"The prevalence of age-related maculopathy by geographic region and ethnicity","volume":"18","author":"Klein","year":"1999","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/j.ophtha.2005.12.013","article-title":"Prevalence of age-related macular degeneration in 4 racial\/ethnic groups in the multi-ethnic study of atherosclerosis","volume":"113","author":"Klein","year":"2006","journal-title":"Ophthalmology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1001\/archopht.1994.01090190080025","article-title":"Heredity and age-related macular degeneration. Observations in monozygotic twins","volume":"112","author":"Klein","year":"1994","journal-title":"Arch. Ophthalmol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1016\/S0002-9394(14)72729-1","article-title":"A twin study of age-related macular degeneration","volume":"120","author":"Meyers","year":"1995","journal-title":"Am. J. Ophthalmol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/S0002-9394(14)71036-0","article-title":"Familial aggregation of age-related maculopathy","volume":"123","author":"Seddon","year":"1997","journal-title":"Am. J. Ophthalmol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1093\/aje\/154.3.207","article-title":"Risk of incident age-related eye diseases in people with an affected sibling: The Beaver Dam Eye Study","volume":"154","author":"Klein","year":"2001","journal-title":"Am. J. Epidemiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1016\/S0161-6420(01)01049-1","article-title":"Genetic influence on early age-related maculopathy: A twin study","volume":"109","author":"Hammond","year":"2002","journal-title":"Ophthalmology"},{"key":"ref_34","first-page":"37","article-title":"Analysis of Hemicentin-1, hOgg1, and E-selectin single nucleotide polymorphisms in age-related macular degeneration","volume":"103","author":"Bojanowski","year":"2005","journal-title":"Trans. Am. Ophthalmol. Soc."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1001\/jamaophthalmol.2016.0669","article-title":"Single-Nucleotide Polymorphisms Associated With Age-Related Macular Degeneration and Lesion Phenotypes in the Comparison of Age-Related Macular Degeneration Treatments Trials","volume":"134","author":"Maguire","year":"2016","journal-title":"JAMA Ophthalmol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1080\/02713683.2016.1196708","article-title":"No Sex Differences in the Frequencies of Common Single Nucleotide Polymorphisms Associated with Age-Related Macular Degeneration","volume":"42","author":"Popp","year":"2017","journal-title":"Curr. Eye Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1001\/jamaophthalmol.2018.1231","article-title":"Association of Single-Nucleotide Polymorphisms in Age-Related Macular Degeneration With Pseudodrusen: Secondary Analysis of Data From the Comparison of AMD Treatments Trials","volume":"136","author":"Lin","year":"2018","journal-title":"JAMA Ophthalmol."},{"key":"ref_38","first-page":"2148","article-title":"A tag-single nucleotide polymorphisms approach to the vascular endothelial growth factor-A gene in age-related macular degeneration","volume":"13","author":"Richardson","year":"2007","journal-title":"Mol. Vis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"17432","DOI":"10.4238\/2015.December.21.13","article-title":"Genome-wide analysis of single nucleotide polymorphisms in patients with atrophic age-related macular degeneration in oldest old Han Chinese","volume":"14","author":"Zhou","year":"2015","journal-title":"Genet. Mol. Res."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Shin, H.T., Yoon, B.W., and Seo, J.H. (2021). Comparison of risk allele frequencies of single nucleotide polymorphisms associated with age-related macular degeneration in different ethnic groups. BMC Ophthalmol., 21.","DOI":"10.1186\/s12886-021-01830-9"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1086\/301901","article-title":"Genetic association of apolipoprotein E with age-related macular degeneration","volume":"63","author":"Klaver","year":"1998","journal-title":"Am. J. Hum. Genet."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.1038\/ng.976","article-title":"A rare penetrant mutation in CFH confers high risk of age-related macular degeneration","volume":"43","author":"Raychaudhuri","year":"2011","journal-title":"Nat. Genet."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1038\/ng.2740","article-title":"A rare nonsynonymous sequence variant in C3 is associated with high risk of age-related macular degeneration","volume":"45","author":"Helgason","year":"2013","journal-title":"Nat. Genet."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1366","DOI":"10.1038\/ng.2741","article-title":"Rare variants in CFI, C3 and C9 are associated with high risk of advanced age-related macular degeneration","volume":"45","author":"Seddon","year":"2013","journal-title":"Nat. Genet."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1038\/ng.2758","article-title":"Identification of a rare coding variant in complement 3 associated with age-related macular degeneration","volume":"45","author":"Zhan","year":"2013","journal-title":"Nat. Genet."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"7401","DOI":"10.1073\/pnas.0912702107","article-title":"Genetic variants near TIMP3 and high-density lipoprotein-associated loci influence susceptibility to age-related macular degeneration","volume":"107","author":"Chen","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"7395","DOI":"10.1073\/pnas.0912019107","article-title":"Genome-wide association study of advanced age-related macular degeneration identifies a role of the hepatic lipase gene (LIPC)","volume":"107","author":"Neale","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3699","DOI":"10.1093\/hmg\/ddr270","article-title":"Common variants near FRK\/COL10A1 and VEGFA are associated with advanced age-related macular degeneration","volume":"20","author":"Yu","year":"2011","journal-title":"Hum. Mol. Genet."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"4663","DOI":"10.1167\/iovs.10-7070","article-title":"Association of variants in the LIPC and ABCA1 genes with intermediate and large drusen and advanced age-related macular degeneration","volume":"52","author":"Yu","year":"2011","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1038\/ng.2578","article-title":"Seven new loci associated with age-related macular degeneration","volume":"45","author":"Fritsche","year":"2013","journal-title":"Nat. Genet."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1038\/ng.3448","article-title":"A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants","volume":"48","author":"Fritsche","year":"2016","journal-title":"Nat. Genet."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1038\/s10038-020-0750-x","article-title":"Genome-wide meta-analysis identifies novel loci associated with age-related macular degeneration","volume":"65","author":"Han","year":"2020","journal-title":"J. Hum. Genet."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1038\/gim.2015.70","article-title":"Age-related macular degeneration: Genome-wide association studies to translation","volume":"18","author":"Black","year":"2016","journal-title":"Genet. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1146\/annurev-genom-090413-025610","article-title":"Age-related macular degeneration: Genetics and biology coming together","volume":"15","author":"Fritsche","year":"2014","journal-title":"Annu. Rev. Genom. Hum. Genet."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Yamashiro, K., Hosoda, Y., Miyake, M., Ooto, S., and Tsujikawa, A. (2020). Characteristics of Pachychoroid Diseases and Age-Related Macular Degeneration: Multimodal Imaging and Genetic Backgrounds. J. Clin. Med., 9.","DOI":"10.3390\/jcm9072034"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1879","DOI":"10.1080\/14656566.2019.1636031","article-title":"Innovative therapies for neovascular age-related macular degeneration","volume":"20","author":"Hussain","year":"2019","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1136\/bjophthalmol-2020-316195","article-title":"Gene therapy for neovascular age-related macular degeneration: Rationale, clinical trials and future directions","volume":"105","author":"Guimaraes","year":"2021","journal-title":"Br. J. Ophthalmol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.preteyeres.2009.11.003","article-title":"The pivotal role of the complement system in aging and age-related macular degeneration: Hypothesis re-visited","volume":"29","author":"Anderson","year":"2010","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1016\/S1350-9462(01)00010-6","article-title":"An integrated hypothesis that considers drusen as biomarkers of immune-mediated processes at the RPE-Bruch\u2019s membrane interface in aging and age-related macular degeneration","volume":"20","author":"Hageman","year":"2001","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1016\/j.ophtha.2020.11.024","article-title":"Genetic Risk, Lifestyle, and Age-Related Macular Degeneration in Europe: The EYE-RISK Consortium","volume":"128","author":"Colijn","year":"2021","journal-title":"Ophthalmology"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1016\/S1286-4579(01)01477-0","article-title":"How the immune system protects the host from infection","volume":"3","author":"Janeway","year":"2001","journal-title":"Microbes Infect."},{"key":"ref_62","first-page":"191","article-title":"Neutrophils and reactive oxygen intermediates mediate glucan-induced pulmonary granuloma formation through the local induction of monocyte chemoattractant protein-1","volume":"76","author":"Kilgore","year":"1997","journal-title":"Lab. Investig."},{"key":"ref_63","first-page":"2903","article-title":"The complement membrane attack complex triggers intracellular Ca2+ fluxes leading to NLRP3 inflammasome activation","volume":"126","author":"Triantafilou","year":"2013","journal-title":"J. Cell Sci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1007\/s12026-012-8381-8","article-title":"Role of C5b-9 complement complex and response gene to complement-32 (RGC-32) in cancer","volume":"56","author":"Vlaicu","year":"2013","journal-title":"Immunol. Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/1755-1536-7-16","article-title":"The role of complement in the pathogenesis of renal ischemia-reperfusion injury and fibrosis","volume":"7","author":"Danobeitia","year":"2014","journal-title":"Fibrogenesis Tissue Repair"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1126\/science.1110189","article-title":"Complement factor H polymorphism and age-related macular degeneration","volume":"308","author":"Edwards","year":"2005","journal-title":"Science"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"7227","DOI":"10.1073\/pnas.0501536102","article-title":"A common haplotype in the complement regulatory gene factor H (HF1\/CFH) predisposes individuals to age-related macular degeneration","volume":"102","author":"Hageman","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1126\/science.1110359","article-title":"Complement factor H variant increases the risk of age-related macular degeneration","volume":"308","author":"Haines","year":"2005","journal-title":"Science"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1126\/science.1109557","article-title":"Complement factor H polymorphism in age-related macular degeneration","volume":"308","author":"Klein","year":"2005","journal-title":"Science"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1086\/431426","article-title":"Strong association of the Y402H variant in complement factor H at 1q32 with susceptibility to age-related macular degeneration","volume":"77","author":"Zareparsi","year":"2005","journal-title":"Am. J. Hum. Genet."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1991","DOI":"10.1093\/hmg\/ddi204","article-title":"Candidate gene analysis suggests a role for fatty acid biosynthesis and regulation of the complement system in the etiology of age-related maculopathy","volume":"14","author":"Conley","year":"2005","journal-title":"Hum. Mol. Genet."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"6063","DOI":"10.1038\/ncomms7063","article-title":"New loci and coding variants confer risk for age-related macular degeneration in East Asians","volume":"6","author":"Cheng","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1007\/s10384-015-0394-0","article-title":"Complement factor H R1210C among Japanese patients with age-related macular degeneration","volume":"59","author":"Miyake","year":"2015","journal-title":"Jpn J. Ophthalmol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"17456","DOI":"10.1073\/pnas.0606234103","article-title":"Individuals homozygous for the age-related macular degeneration risk-conferring variant of complement factor H have elevated levels of CRP in the choroid","volume":"103","author":"Johnson","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"3831","DOI":"10.4049\/jimmunol.178.6.3831","article-title":"Y402H polymorphism of complement factor H affects binding affinity to C-reactive protein","volume":"178","author":"Laine","year":"2007","journal-title":"J. Immunol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"6873","DOI":"10.1167\/iovs.15-17432","article-title":"Rare Variants in the Functional Domains of Complement Factor H Are Associated With Age-Related Macular Degeneration","volume":"56","author":"Triebwasser","year":"2015","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.molimm.2004.02.005","article-title":"The human complement factor H: Functional roles, genetic variations and disease associations","volume":"41","year":"2004","journal-title":"Mol. Immunol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"17087","DOI":"10.1016\/S0021-9258(18)41897-2","article-title":"Formation and structure of the C5b-7 complex of the lytic pathway of complement","volume":"267","author":"DiScipio","year":"1992","journal-title":"J. Biol. Chem."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"10996","DOI":"10.1073\/pnas.93.20.10996","article-title":"Identification of three physically and functionally distinct binding sites for C3b in human complement factor H by deletion mutagenesis","volume":"93","author":"Sharma","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"3398","DOI":"10.1016\/j.molimm.2007.02.012","article-title":"Defective complement control of factor H (Y402H) and FHL-1 in age-related macular degeneration","volume":"44","author":"Skerka","year":"2007","journal-title":"Mol. Immunol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"3949","DOI":"10.1021\/bi4003452","article-title":"Functional anatomy of complement factor H","volume":"52","author":"Makou","year":"2013","journal-title":"Biochemistry"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"22889","DOI":"10.1038\/srep22889","article-title":"Complement factor H binding of monomeric C-reactive protein downregulates proinflammatory activity and is impaired with at risk polymorphic CFH variants","volume":"6","author":"Molins","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.immuni.2017.01.006","article-title":"Complement Factor H Inhibits CD47-Mediated Resolution of Inflammation","volume":"46","author":"Calippe","year":"2017","journal-title":"Immunity"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1002\/path.5867","article-title":"Local factor H production by human choroidal endothelial cells mitigates complement deposition: Implications for macular degeneration","volume":"257","author":"Mulfaul","year":"2022","journal-title":"J. Pathol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"30192","DOI":"10.1074\/jbc.M110.103986","article-title":"Impaired binding of the age-related macular degeneration-associated complement factor H 402H allotype to Bruch\u2019s membrane in human retina","volume":"285","author":"Clark","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"13873","DOI":"10.1038\/s41598-019-50420-9","article-title":"CFH exerts anti-oxidant effects on retinal pigment epithelial cells independently from protecting against membrane attack complex","volume":"9","author":"Borras","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"10320","DOI":"10.1038\/s41598-020-67292-z","article-title":"Loss of Complement Factor H impairs antioxidant capacity and energy metabolism of human RPE cells","volume":"10","author":"Armento","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1038\/nature10449","article-title":"Complement factor H binds malondialdehyde epitopes and protects from oxidative stress","volume":"478","author":"Weismann","year":"2011","journal-title":"Nature"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"3703","DOI":"10.1073\/pnas.1814014116","article-title":"Human complement factor H Y402H polymorphism causes an age-related macular degeneration phenotype and lipoprotein dysregulation in mice","volume":"116","author":"Landowski","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1001\/jamaophthalmol.2016.4604","article-title":"The Functional Effect of Rare Variants in Complement Genes on C3b Degradation in Patients With Age-Related Macular Degeneration","volume":"135","author":"Geerlings","year":"2017","journal-title":"JAMA Ophthalmol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1038\/ng1873","article-title":"Common variation in three genes, including a noncoding variant in CFH, strongly influences risk of age-related macular degeneration","volume":"38","author":"Maller","year":"2006","journal-title":"Nat. Genet."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"7532507","DOI":"10.1155\/2018\/7532507","article-title":"Complement System and Age-Related Macular Degeneration: Implications of Gene-Environment Interaction for Preventive and Personalized Medicine","volume":"2018","author":"Maugeri","year":"2018","journal-title":"Biomed. Res. Int."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1136\/bjophthalmol-2017-311384","article-title":"Genetic risk factors for late age-related macular degeneration in India","volume":"102","author":"Rajendran","year":"2018","journal-title":"Br. J. Ophthalmol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1136\/bjophthalmol-2017-311673","article-title":"Prevalence of age-related macular degeneration associated genetic risk factors and 4-year progression data in the Irish population","volume":"102","author":"Connolly","year":"2018","journal-title":"Br. J. Ophthalmol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.2147\/OPTH.S298310","article-title":"Associations of ARMS2 and CFH Gene Polymorphisms with Neovascular Age-Related Macular Degeneration","volume":"15","author":"Supanji","year":"2021","journal-title":"Clin. Ophthalmol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"e691","DOI":"10.1111\/aos.14357","article-title":"An association of neovascular age-related macular degeneration with polymorphisms of CFH, ARMS2, HTRA1 and C3 genes in Czech population","volume":"98","author":"Matuskova","year":"2020","journal-title":"Acta Ophthalmol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1177\/11206721211002698","article-title":"Gene polymorphisms associated with an increased risk of exudative age-related macular degeneration in a Spanish population","volume":"32","author":"Gili","year":"2022","journal-title":"Eur. J. Ophthalmol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1007\/s10792-019-01274-7","article-title":"Investigation of genetic base in the treatment of age-related macular degeneration","volume":"40","author":"Gourgouli","year":"2020","journal-title":"Int. Ophthalmol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"2290","DOI":"10.1177\/15353702211024543","article-title":"Association of genetic variants rs641153 (CFB), rs2230199 (C3), and rs1410996 (CFH) with age-related macular degeneration in a Brazilian population","volume":"246","author":"Neto","year":"2021","journal-title":"Exp. Biol. Med."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1093\/aje\/kwj279","article-title":"Association between apolipoprotein E polymorphisms and age-related macular degeneration: A HuGE review and meta-analysis","volume":"164","author":"Thakkinstian","year":"2006","journal-title":"Am. J. Epidemiol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1016\/j.ophtha.2017.12.023","article-title":"Genome-Wide Association Study Reveals Variants in CFH and CFHR4 Associated with Systemic Complement Activation: Implications in Age-Related Macular Degeneration","volume":"125","author":"Paun","year":"2018","journal-title":"Ophthalmology"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"e669","DOI":"10.1111\/aos.14970","article-title":"Genetic associations of anti-vascular endothelial growth factor therapy response in age-related macular degeneration: A systematic review and meta-analysis","volume":"100","author":"Wang","year":"2022","journal-title":"Acta Ophthalmol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"5283","DOI":"10.1093\/hmg\/ddu226","article-title":"Whole-exome sequencing identifies rare, functional CFH variants in families with macular degeneration","volume":"23","author":"Yu","year":"2014","journal-title":"Hum. Mol. Genet."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"(2018). Association Between Complement Factor C2\/C3\/CFB\/CFH Polymorphisms and Age-Related Macular Degeneration: A Meta-Analysis. Genet. Test. Mol. Biomark., 22, 526\u2013540.","DOI":"10.1089\/gtmb.2018.0110"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"06001","DOI":"10.1051\/bioconf\/20214106001","article-title":"rs3753394 Complement Factor H (CFH) Gene Polymorphism in Patients with Age-Related Macular Degeneration (AMD) in Indonesian Population","volume":"41","author":"Supanji","year":"2021","journal-title":"BIO Web Conf."},{"key":"ref_106","first-page":"285","article-title":"Analysis of rare variants in the CFH gene in patients with the cuticular drusen subtype of age-related macular degeneration","volume":"21","author":"Duvvari","year":"2015","journal-title":"Mol. Vis."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1001\/jamaophthalmol.2015.0814","article-title":"Phenotypic Characterization of Complement Factor H R1210C Rare Genetic Variant in Age-Related Macular Degeneration","volume":"133","author":"Ferrara","year":"2015","journal-title":"JAMA Ophthalmol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.survophthal.2017.05.003","article-title":"Systemic and ocular fluid compounds as potential biomarkers in age-related macular degeneration","volume":"63","author":"Kersten","year":"2018","journal-title":"Surv. Ophthalmol."},{"key":"ref_109","first-page":"5276","article-title":"Protective coding variants in CFH and PELI3 and a variant near CTRB1 are associated with age-related macular degenerationdagger","volume":"25","author":"Yu","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"100087","DOI":"10.1016\/j.xops.2021.100087","article-title":"Genetic Risk in Families with Age-Related Macular Degeneration","volume":"1","author":"Lechanteur","year":"2021","journal-title":"Ophthalmol. Sci."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1016\/j.ophtha.2008.01.036","article-title":"CFH and LOC387715\/ARMS2 genotypes and treatment with antioxidants and zinc for age-related macular degeneration","volume":"115","author":"Klein","year":"2008","journal-title":"Ophthalmology"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.ophtha.2014.07.049","article-title":"Treatment response to antioxidants and zinc based on CFH and ARMS2 genetic risk allele number in the Age-Related Eye Disease Study","volume":"122","author":"Awh","year":"2015","journal-title":"Ophthalmology"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1136\/bjophthalmol-2016-308624","article-title":"Response to AREDS supplements according to genetic factors: Survival analysis approach using the eye as the unit of analysis","volume":"100","author":"Seddon","year":"2016","journal-title":"Br. J. Ophthalmol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1167\/iovs.08-2514","article-title":"Peripheral retinal drusen and reticular pigment: Association with CFHY402H and CFHrs1410996 genotypes in family and twin studies","volume":"50","author":"Seddon","year":"2009","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_115","first-page":"75","article-title":"Geographic distribution of rare variants associated with age-related macular degeneration","volume":"24","author":"Geerlings","year":"2018","journal-title":"Mol. Vis."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1038\/ejhg.2008.140","article-title":"Variation near complement factor I is associated with risk of advanced AMD","volume":"17","author":"Fagerness","year":"2009","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1038\/ng.2640","article-title":"A functional variant in the CFI gene confers a high risk of age-related macular degeneration","volume":"45","author":"Nilsson","year":"2013","journal-title":"Nat. Genet."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1167\/iovs.61.6.18","article-title":"Rare Genetic Variants in Complement Factor I Lead to Low FI Plasma Levels Resulting in Increased Risk of Age-Related Macular Degeneration","volume":"61","author":"Hallam","year":"2020","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1167\/tvst.9.9.37","article-title":"Functional Analysis of Rare Genetic Variants in Complement Factor I (CFI) using a Serum-Based Assay in Advanced Age-related Macular Degeneration","volume":"9","author":"Java","year":"2020","journal-title":"Transl. Vis. Sci. Technol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"2313","DOI":"10.1093\/hmg\/ddaa114","article-title":"Effect of rare coding variants in the CFI gene on Factor I expression levels","volume":"29","author":"Volokhina","year":"2020","journal-title":"Hum. Mol. Genet."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.molimm.2016.11.016","article-title":"The complement system in age-related macular degeneration: A review of rare genetic variants and implications for personalized treatment","volume":"84","author":"Geerlings","year":"2017","journal-title":"Mol. Immunol."},{"key":"ref_122","first-page":"2295","article-title":"GT005, a gene therapy for the treatment of dry age-related macular degeneration (AMD)","volume":"61","author":"Ellis","year":"2020","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1038\/ng2131","article-title":"Variation in complement factor 3 is associated with risk of age-related macular degeneration","volume":"39","author":"Maller","year":"2007","journal-title":"Nat. Genet."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1056\/NEJMoa072618","article-title":"Complement C3 variant and the risk of age-related macular degeneration","volume":"357","author":"Yates","year":"2007","journal-title":"N. Engl. J. Med."},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Zhang, J., Li, S., Hu, S., Yu, J., and Xiang, Y. (2018). Association between genetic variation of complement C3 and the susceptibility to advanced age-related macular degeneration: A meta-analysis. BMC Ophthalmol., 18.","DOI":"10.1186\/s12886-018-0945-5"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"8761","DOI":"10.1073\/pnas.1019338108","article-title":"Common polymorphisms in C3, factor B, and factor H collaborate to determine systemic complement activity and disease risk","volume":"108","author":"Heurich","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_127","doi-asserted-by":"crossref","unstructured":"Duvvari, M.R., Paun, C.C., Buitendijk, G.H., Saksens, N.T., Volokhina, E.B., Ristau, T., Schoenmaker-Koller, F.E., van de Ven, J.P., Groenewoud, J.M., and van den Heuvel, L.P. (2014). Analysis of rare variants in the C3 gene in patients with age-related macular degeneration. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0094165"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1080\/02713680903003484","article-title":"Association of c3 gene polymorphisms with neovascular age-related macular degeneration in a chinese population","volume":"34","author":"Pei","year":"2009","journal-title":"Curr. Eye Res."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.ophtha.2019.07.011","article-title":"Complement C3 Inhibitor Pegcetacoplan for Geographic Atrophy Secondary to Age-Related Macular Degeneration: A Randomized Phase 2 Trial","volume":"127","author":"Liao","year":"2020","journal-title":"Ophthalmology"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/S0002-9394(02)01624-0","article-title":"A role for local inflammation in the formation of drusen in the aging eye","volume":"134","author":"Anderson","year":"2002","journal-title":"Am. J. Ophthalmol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1006\/exer.1999.0798","article-title":"A potential role for immune complex pathogenesis in drusen formation","volume":"70","author":"Johnson","year":"2000","journal-title":"Exp. Eye Res."},{"key":"ref_132","doi-asserted-by":"crossref","unstructured":"Scholl, H.P., Charbel Issa, P., Walier, M., Janzer, S., Pollok-Kopp, B., Borncke, F., Fritsche, L.G., Chong, N.V., Fimmers, R., and Wienker, T. (2008). Systemic complement activation in age-related macular degeneration. PLoS ONE, 3.","DOI":"10.1371\/annotation\/32b9bc31-ed6d-4d31-9ce0-480407017bad"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"2328","DOI":"10.1073\/pnas.0408835103","article-title":"Drusen complement components C3a and C5a promote choroidal neovascularization","volume":"103","author":"Nozaki","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1016\/j.ophtha.2009.08.032","article-title":"The complement component 5 gene and age-related macular degeneration","volume":"117","author":"Baas","year":"2010","journal-title":"Ophthalmology"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1186\/s40662-019-0161-2","article-title":"Evaluation of the association of C5 with neovascular age-related macular degeneration and polypoidal choroidal vasculopathy","volume":"6","author":"Liu","year":"2019","journal-title":"Eye Vis."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1016\/j.ophtha.2020.08.027","article-title":"C5 Inhibitor Avacincaptad Pegol for Geographic Atrophy Due to Age-Related Macular Degeneration: A Randomized Pivotal Phase 2\/3 Trial","volume":"128","author":"Jaffe","year":"2021","journal-title":"Ophthalmology"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1001\/jamaophthalmol.2015.5592","article-title":"Rare Genetic Variants Associated With Development of Age-Related Macular Degeneration","volume":"134","author":"Saksens","year":"2016","journal-title":"JAMA Ophthalmol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"2022","DOI":"10.1093\/hmg\/ddaa057","article-title":"Family-based exome sequencing identifies rare coding variants in age-related macular degeneration","volume":"29","author":"Ratnapriya","year":"2020","journal-title":"Hum Mol. Genet."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"1188","DOI":"10.1093\/hmg\/ddab086","article-title":"The rare C9 P167S risk variant for age-related macular degeneration increases polymerization of the terminal component of the complement cascade","volume":"30","author":"McMahon","year":"2021","journal-title":"Hum. Mol. Genet."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"2678","DOI":"10.1093\/hmg\/ddy178","article-title":"Functional analyses of rare genetic variants in complement component C9 identified in patients with age-related macular degeneration","volume":"27","author":"Kremlitzka","year":"2018","journal-title":"Hum. Mol. Genet."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.4049\/jimmunol.160.3.1509","article-title":"A non-sense mutation at Arg95 is predominant in complement 9 deficiency in Japanese","volume":"160","author":"Horiuchi","year":"1998","journal-title":"J. Immunol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1167\/iovs.11-8425","article-title":"C9-R95X polymorphism in patients with neovascular age-related macular degeneration","volume":"53","author":"Nishiguchi","year":"2012","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1038\/ng1750","article-title":"Variation in factor B (BF) and complement component 2 (C2) genes is associated with age-related macular degeneration","volume":"38","author":"Gold","year":"2006","journal-title":"Nat. Genet."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"12","DOI":"10.3109\/13816810.2013.766217","article-title":"Complement factor B polymorphism and the phenotype of early age-related macular degeneration","volume":"35","author":"Mantel","year":"2014","journal-title":"Ophthalmic. Genet."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"1986","DOI":"10.1093\/hmg\/ddm146","article-title":"Protective effect of complement factor B and complement component 2 variants in age-related macular degeneration","volume":"16","author":"Spencer","year":"2007","journal-title":"Hum. Mol. Genet."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"259","DOI":"10.3109\/02713683.2011.635401","article-title":"CFB\/C2 gene polymorphisms and risk of age-related macular degeneration: A systematic review and meta-analysis","volume":"37","author":"Sun","year":"2012","journal-title":"Curr. Eye Res."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1093\/aje\/kws031","article-title":"The association between complement component 2\/complement factor B polymorphisms and age-related macular degeneration: A HuGE review and meta-analysis","volume":"176","author":"Thakkinstian","year":"2012","journal-title":"Am. J. Epidemiol."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1001\/archophthalmol.2010.18","article-title":"Complement, age-related macular degeneration and a vision of the future","volume":"128","author":"Gehrs","year":"2010","journal-title":"Arch. Ophthalmol."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1007\/BF00215259","article-title":"Allelic differences in hemolytic activity and protein concentration of BF molecules are found in association with particular HLA haplotypes","volume":"34","author":"Lokki","year":"1991","journal-title":"Immunogenetics"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"7188","DOI":"10.1038\/s41598-020-64301-z","article-title":"Genetic factors associated with response to as-needed aflibercept therapy for typical neovascular age-related macular degeneration and polypoidal choroidal vasculopathy","volume":"10","author":"Yoneyama","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1167\/iovs.11-8468","article-title":"Significance of C2\/CFB variants in age-related macular degeneration and polypoidal choroidal vasculopathy in a Japanese population","volume":"53","author":"Nakata","year":"2012","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"1816","DOI":"10.1126\/science.1195821","article-title":"Structures of C3b in complex with factors B and D give insight into complement convertase formation","volume":"330","author":"Forneris","year":"2010","journal-title":"Science"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"8828","DOI":"10.1167\/iovs.11-7933","article-title":"Complement factor D in age-related macular degeneration","volume":"52","author":"Stanton","year":"2011","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_154","first-page":"2273","article-title":"Lack of association of CFD polymorphisms with advanced age-related macular degeneration","volume":"16","author":"Zeng","year":"2010","journal-title":"Mol. Vis."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1001\/jamaophthalmol.2018.1544","article-title":"Efficacy and Safety of Lampalizumab for Geographic Atrophy Due to Age-Related Macular Degeneration: Chroma and Spectri Phase 3 Randomized Clinical Trials","volume":"136","author":"Holz","year":"2018","journal-title":"JAMA Ophthalmol."},{"key":"ref_156","first-page":"61","article-title":"Ultrastructure of the choroid. Its role in the pathogenesis of chorioretinal disease","volume":"42","author":"Hogan","year":"1961","journal-title":"Trans. Pac. Coast Otoophthalmol. Soc. Annu. Meet"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.preteyeres.2009.08.003","article-title":"The dynamic nature of Bruch\u2019s membrane","volume":"29","author":"Booij","year":"2010","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1096\/fasebj.12.12.1075","article-title":"Matrix metalloproteinases: Structures, evolution, and diversification","volume":"12","author":"Massova","year":"1998","journal-title":"FASEB J."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"4459","DOI":"10.1167\/iovs.10-6678","article-title":"Disturbed matrix metalloproteinase activity of Bruch\u2019s membrane in age-related macular degeneration","volume":"52","author":"Hussain","year":"2011","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_160","doi-asserted-by":"crossref","unstructured":"Garcia-Onrubia, L., Valentin-Bravo, F.J., Coco-Martin, R.M., Gonzalez-Sarmiento, R., Pastor, J.C., Usategui-Martin, R., and Pastor-Idoate, S. (2020). Matrix Metalloproteinases in Age-Related Macular Degeneration (AMD). Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21165934"},{"key":"ref_161","first-page":"2676","article-title":"Age-dependent variation in metalloproteinase activity of isolated human Bruch\u2019s membrane and choroid","volume":"40","author":"Guo","year":"1999","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_162","first-page":"2367","article-title":"TIMP-3 in Bruch\u2019s membrane: Changes during aging and in age-related macular degeneration","volume":"40","author":"Kamei","year":"1999","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1111\/aos.13894","article-title":"Imbalances in tissue inhibitors of metalloproteinases differentiate choroidal neovascularization from geographic atrophy","volume":"97","author":"Subhi","year":"2019","journal-title":"Acta Ophthalmol."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1086\/382786","article-title":"Age-related macular degeneration: A high-resolution genome scan for susceptibility loci in a population enriched for late-stage disease","volume":"74","author":"Abecasis","year":"2004","journal-title":"Am. J. Hum. Genet."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.preteyeres.2013.07.003","article-title":"Aging is not a disease: Distinguishing age-related macular degeneration from aging","volume":"37","author":"Ardeljan","year":"2013","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_166","first-page":"1921","article-title":"Localization of TIMP-3 mRNA expression to the retinal pigment epithelium","volume":"37","author":"Della","year":"1996","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"31226","DOI":"10.1074\/jbc.M000907200","article-title":"TIMP-3 binds to sulfated glycosaminoglycans of the extracellular matrix","volume":"275","author":"Yu","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_168","first-page":"323","article-title":"Tissue inhibitor of metalloproteinases-3 is a component of Bruch\u2019s membrane of the eye","volume":"150","author":"Fariss","year":"1997","journal-title":"Am. J. Pathol."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.matbio.2015.03.005","article-title":"The role of TIMPs in regulation of extracellular matrix proteolysis","volume":"44\u201346","author":"Arpino","year":"2015","journal-title":"Matrix Biol."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1006\/exer.2001.1089","article-title":"Measurement of TIMP-3 expression and Bruch\u2019s membrane thickness in human macula","volume":"73","author":"Bailey","year":"2001","journal-title":"Exp. Eye Res."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1038\/nm846","article-title":"A novel function for tissue inhibitor of metalloproteinases-3 (TIMP3): Inhibition of angiogenesis by blockage of VEGF binding to VEGF receptor-2","volume":"9","author":"Qi","year":"2003","journal-title":"Nat. Med."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1038\/ng0694-158","article-title":"Sorsby\u2019s fundus dystrophy is genetically linked to chromosome 22q13-qter","volume":"7","author":"Weber","year":"1994","journal-title":"Nat. Genet."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.molimm.2018.12.026","article-title":"TIMP-3 suppression induces choroidal neovascularization by moderating the polarization of macrophages in age-related macular degeneration","volume":"106","author":"Cheng","year":"2019","journal-title":"Mol. Immunol."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"S9","DOI":"10.1007\/s11605-009-1014-4","article-title":"Emerging concepts of bile reflux in the constellation of gastroesophageal reflux disease","volume":"14","author":"Kauer","year":"2010","journal-title":"J. Gastrointest. Surg."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"7812","DOI":"10.18632\/oncotarget.23241","article-title":"Uncovering genetic and non-genetic biomarkers specific for exudative age-related macular degeneration: Significant association of twelve variants","volume":"9","author":"Cascella","year":"2018","journal-title":"Oncotarget"},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"5525","DOI":"10.1167\/iovs.10-6827","article-title":"Evaluation of serum lipid concentrations and genetic variants at high-density lipoprotein metabolism loci and TIMP3 in age-related macular degeneration","volume":"52","author":"Fauser","year":"2011","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"27","DOI":"10.3109\/09273948.2011.628432","article-title":"Genetics of immunological and inflammatory components in age-related macular degeneration","volume":"20","author":"Tuo","year":"2012","journal-title":"Ocul. Immunol. Inflamm."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"139","DOI":"10.3109\/13816810.2011.643440","article-title":"An rs9621532 variant near the TIMP3 gene is not associated with neovascular age-related macular degeneration and polypoidal choroidal vasculopathy in a Chinese Han population","volume":"33","author":"Zeng","year":"2012","journal-title":"Ophthalmic Genet."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"9602949","DOI":"10.1155\/2019\/9602949","article-title":"Haplotypes of HTRA1 rs1120638, TIMP3 rs9621532, VEGFA rs833068, CFI rs10033900, ERCC6 rs3793784, and KCTD10 rs56209061 Gene Polymorphisms in Age-Related Macular Degeneration","volume":"2019","author":"Liutkeviciene","year":"2019","journal-title":"Dis. Markers"},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1038\/ejhg.2013.14","article-title":"Influence of TIMP3\/SYN3 polymorphisms on the phenotypic presentation of age-related macular degeneration","volume":"21","author":"Ardeljan","year":"2013","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"217","DOI":"10.3109\/13816810.2013.781192","article-title":"The role of MMP2 (-1306C>T) and TIMP2 (-418 G>C) promoter variants in age-related macular degeneration","volume":"34","author":"Ortak","year":"2013","journal-title":"Ophthalmic Genet"},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1080\/13816810.2018.1525752","article-title":"Association analysis of genetic polymorphisms and expression levels of selected genes involved in extracellular matrix turnover and angiogenesis with the risk of age-related macular degeneration","volume":"39","author":"Oszajca","year":"2018","journal-title":"Ophthalmic Genet."},{"key":"ref_183","first-page":"1349","article-title":"MMP-2 Rs24386 (C-->T) gene polymorphism and the phenotype of age-related macular degeneration","volume":"10","author":"Liutkeviciene","year":"2017","journal-title":"Int. J. Ophthalmol."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"149","DOI":"10.3109\/13816810.2013.838274","article-title":"The Role of Matrix Metalloproteinases Polymorphisms in Age-Related Macular Degeneration","volume":"36","author":"Liutkeviciene","year":"2015","journal-title":"Ophthalmic Genet."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"551","DOI":"10.4103\/ijo.IJO_1050_17","article-title":"Association of exudative age-related macular degeneration with matrix metalloproteinases-2 (-1306 C\/T) rs243865 gene polymorphism","volume":"66","author":"Liutkeviciene","year":"2018","journal-title":"Indian J. Ophthalmol."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1093\/aje\/kwn024","article-title":"Estrogen receptor \u03b1 and matrix metalloproteinase 2 polymorphisms and age-related maculopathy in older women","volume":"167","author":"Seitzman","year":"2008","journal-title":"Am. J. Epidemiol."},{"key":"ref_187","doi-asserted-by":"crossref","unstructured":"Usategui-Martin, R., Pastor-Idoate, S., Chamorro, A.J., Fernandez, I., Fernandez-Bueno, I., Marcos-Martin, M., Gonzalez-Sarmiento, R., and Carlos Pastor, J. (2019). Meta-analysis of the rs243865 MMP-2 polymorphism and age-related macular degeneration risk. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0213624"},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"e8190","DOI":"10.1097\/MD.0000000000008190","article-title":"Risk of macular degeneration affected by polymorphisms in Matrix metalloproteinase-2: A case-control study in Chinese Han population","volume":"96","author":"Cheng","year":"2017","journal-title":"Medicine"},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1093\/hmg\/ddy002","article-title":"Genome-wide analysis of disease progression in age-related macular degeneration","volume":"27","author":"Yan","year":"2018","journal-title":"Hum. Mol. Genet."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"100002","DOI":"10.1016\/j.xops.2020.100002","article-title":"Genetic Association between MMP9 and Choroidal Neovascularization in Age-Related Macular Degeneration","volume":"1","author":"Sohn","year":"2021","journal-title":"Ophthalmol. Sci."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1097\/01.GIM.0000159903.69597.73","article-title":"MMP-9 microsatellite polymorphism and susceptibility to exudative form of age-related macular degeneration","volume":"7","author":"Fiotti","year":"2005","journal-title":"Genet. Med."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1080\/13816810.2018.1484928","article-title":"The association of matrix metalloproteinases polymorphisms and interleukins in advanced age-related macular degeneration","volume":"39","author":"Budiene","year":"2018","journal-title":"Ophthalmic Genet."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"404","DOI":"10.3390\/medicina48080060","article-title":"Does matrix metalloproteinase-3 polymorphism play a role in age-related macular degeneration in patients with myocardial infarction?","volume":"48","author":"Liutkeviciene","year":"2012","journal-title":"Medicina"},{"key":"ref_194","first-page":"2636","article-title":"Tissue distribution of type VIII collagen in human adult and fetal eyes","volume":"32","author":"Tamura","year":"1991","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1016\/j.ophtha.2018.03.040","article-title":"Whole-Exome Sequencing in Age-Related Macular Degeneration Identifies Rare Variants in COL8A1, a Component of Bruch\u2019s Membrane","volume":"125","author":"Corominas","year":"2018","journal-title":"Ophthalmology"},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"1422","DOI":"10.1016\/j.ophtha.2019.04.033","article-title":"Complement Factor H Gene Mutations: Implications for Genetic Testing and Precision Medicine in Macular Degeneration","volume":"126","author":"Hoyng","year":"2019","journal-title":"Ophthalmology"},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1007\/s00439-010-0904-6","article-title":"Genome-wide analysis of copy number variants in age-related macular degeneration","volume":"129","author":"Meyer","year":"2011","journal-title":"Hum. Genet."},{"key":"ref_198","first-page":"2435","article-title":"Spectral profiling of autofluorescence associated with lipofuscin, Bruch\u2019s Membrane, and sub-RPE deposits in normal and AMD eyes","volume":"43","author":"Marmorstein","year":"2002","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.preteyeres.2018.04.006","article-title":"A new perspective on lipid research in age-related macular degeneration","volume":"67","author":"Emri","year":"2018","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"AMD182","DOI":"10.1167\/iovs.18-24883","article-title":"Antecedents of Soft Drusen, the Specific Deposits of Age-Related Macular Degeneration, in the Biology of Human Macula","volume":"59","author":"Curcio","year":"2018","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1038\/eye.2001.140","article-title":"Photoreceptor topography in ageing and age-related maculopathy","volume":"15","author":"Curcio","year":"2001","journal-title":"Eye"},{"key":"ref_202","first-page":"265","article-title":"Accumulation of cholesterol with age in human Bruch\u2019s membrane","volume":"42","author":"Curcio","year":"2001","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"AMD160","DOI":"10.1167\/iovs.18-24882","article-title":"Soft Drusen in Age-Related Macular Degeneration: Biology and Targeting Via the Oil Spill Strategies","volume":"59","author":"Curcio","year":"2018","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"14682","DOI":"10.1073\/pnas.222551899","article-title":"Drusen proteome analysis: An approach to the etiology of age-related macular degeneration","volume":"99","author":"Crabb","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.preteyeres.2009.08.001","article-title":"Aging, age-related macular degeneration, and the response-to-retention of apolipoprotein B-containing lipoproteins","volume":"28","author":"Curcio","year":"2009","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1096\/fasebj.14.7.835","article-title":"Drusen associated with aging and age-related macular degeneration contain proteins common to extracellular deposits associated with atherosclerosis, elastosis, amyloidosis, and dense deposit disease","volume":"14","author":"Mullins","year":"2000","journal-title":"FASEB J."},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.ophtha.2009.07.014","article-title":"Reticular pseudodrusen are subretinal drusenoid deposits","volume":"117","author":"Zweifel","year":"2010","journal-title":"Ophthalmology"},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"1775","DOI":"10.1016\/j.ophtha.2010.01.027","article-title":"Prevalence and significance of subretinal drusenoid deposits (reticular pseudodrusen) in age-related macular degeneration","volume":"117","author":"Zweifel","year":"2010","journal-title":"Ophthalmology"},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1056\/NEJM199901143400207","article-title":"Atherosclerosis\u2014an inflammatory disease","volume":"340","author":"Ross","year":"1999","journal-title":"N. Engl. J. Med."},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1038\/nri3793","article-title":"Cholesterol, inflammation and innate immunity","volume":"15","author":"Tall","year":"2015","journal-title":"Nat. Rev. Immunol."},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1038\/35025203","article-title":"Atherosclerosis","volume":"407","author":"Lusis","year":"2000","journal-title":"Nature"},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"2071","DOI":"10.1161\/ATVBAHA.108.168690","article-title":"High-density lipoprotein reduces the human monocyte inflammatory response","volume":"28","author":"Murphy","year":"2008","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1093\/ajcn\/85.3.762","article-title":"Effect of dietary lutein and zeaxanthin on plasma carotenoids and their transport in lipoproteins in age-related macular degeneration","volume":"85","author":"Wang","year":"2007","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1016\/S0022-2275(20)34443-6","article-title":"Plasma lipoproteins: Apolipoprotein structure and function","volume":"25","author":"Mahley","year":"1984","journal-title":"J. Lipid Res."},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1126\/science.3283935","article-title":"Apolipoprotein E: Cholesterol transport protein with expanding role in cell biology","volume":"240","author":"Mahley","year":"1988","journal-title":"Science"},{"key":"ref_216","first-page":"11","article-title":"Human apolipoprotein E isoprotein subclasses are genetically determined","volume":"33","author":"Zannis","year":"1981","journal-title":"Am. J. Hum. Genet."},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1001\/jama.1997.03550160069041","article-title":"Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium","volume":"278","author":"Farrer","year":"1997","journal-title":"JAMA"},{"key":"ref_218","first-page":"145","article-title":"Genetic mutations affecting human lipoproteins, their receptors, and their enzymes","volume":"21","author":"Zannis","year":"1993","journal-title":"Adv. Hum. Genet."},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/S0002-9394(99)80146-9","article-title":"The epsilon4 allele of the apolipoprotein E gene as a potential protective factor for exudative age-related macular degeneration","volume":"125","author":"Souied","year":"1998","journal-title":"Am. J. Ophthalmol."},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1076\/opge.23.4.209.13883","article-title":"A pooled case-control study of the apolipoprotein E (APOE) gene in age-related maculopathy","volume":"23","author":"Schmidt","year":"2002","journal-title":"Ophthalmic Genet."},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.1167\/iovs.03-1253","article-title":"Association of apolipoprotein E alleles with susceptibility to age-related macular degeneration in a large cohort from a single center","volume":"45","author":"Zareparsi","year":"2004","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1002\/humu.21577","article-title":"Evidence of association of APOE with age-related macular degeneration: A pooled analysis of 15 studies","volume":"32","author":"McKay","year":"2011","journal-title":"Hum. Mutat."},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"4290","DOI":"10.1167\/iovs.15-16533","article-title":"Differences in the Genetic Susceptibility to Age-Related Macular Degeneration Clinical Subtypes","volume":"56","author":"Shen","year":"2015","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1016\/j.arcmed.2017.08.002","article-title":"Association of Apolipoprotein E Polymorphisms with Age-related Macular Degeneration Subtypes: An Updated Systematic Review and Meta-analysis","volume":"48","author":"Xiying","year":"2017","journal-title":"Arch. Med. Res."},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.1177\/1535370220985466","article-title":"Evaluation of APOE polymorphisms and the risk for age-related macular degeneration in a Southeastern Brazilian population","volume":"246","author":"Viturino","year":"2021","journal-title":"Exp. Biol. Med."},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1080\/13816810.2018.1479429","article-title":"The role of apolipoprotein E (rs7412 and rs429358) in age-related macular degeneration","volume":"39","author":"Liutkeviciene","year":"2018","journal-title":"Ophthalmic Genet."},{"key":"ref_227","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1002\/humu.20288","article-title":"Apolipoprotein (APOE) gene is associated with progression of age-related macular degeneration (AMD)","volume":"27","author":"Baird","year":"2006","journal-title":"Hum. Mutat."},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1093\/aje\/kwr329","article-title":"Apolipoprotein E gene associations in age-related macular degeneration: The Melbourne Collaborative Cohort Study","volume":"175","author":"Adams","year":"2012","journal-title":"Am. J. Epidemiol."},{"key":"ref_229","doi-asserted-by":"crossref","unstructured":"Holliday, E.G., Smith, A.V., Cornes, B.K., Buitendijk, G.H., Jensen, R.A., Sim, X., Aspelund, T., Aung, T., Baird, P.N., and Boerwinkle, E. (2013). Insights into the genetic architecture of early stage age-related macular degeneration: A genome-wide association study meta-analysis. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0053830"},{"key":"ref_230","doi-asserted-by":"crossref","first-page":"2770","DOI":"10.1016\/j.sjbs.2020.06.037","article-title":"APOE2 promotes the development and progression of subretinal neovascularization in age-related macular degeneration via MAPKs signaling pathway","volume":"27","author":"Sun","year":"2020","journal-title":"Saudi J. Biol. Sci."},{"key":"ref_231","doi-asserted-by":"crossref","first-page":"4532","DOI":"10.1073\/pnas.94.9.4532","article-title":"A hepatic lipase (LIPC) allele associated with high plasma concentrations of high density lipoprotein cholesterol","volume":"94","author":"Guerra","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_232","first-page":"1343","article-title":"Hepatic Lipase C knockout mouse has diminished ERGs and Bruch\u2019s lipid deposits","volume":"60","author":"Chavali","year":"2019","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_233","doi-asserted-by":"crossref","first-page":"1989","DOI":"10.1016\/j.ophtha.2010.07.009","article-title":"Serum lipid biomarkers and hepatic lipase gene associations with age-related macular degeneration","volume":"117","author":"Reynolds","year":"2010","journal-title":"Ophthalmology"},{"key":"ref_234","doi-asserted-by":"crossref","first-page":"15711","DOI":"10.1038\/srep15711","article-title":"CETP\/LPL\/LIPC gene polymorphisms and susceptibility to age-related macular degeneration","volume":"5","author":"Wang","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_235","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.gene.2018.11.004","article-title":"SIRT1 rs12778366, FGFR2 rs2981582, STAT3 rs744166, LIPC rs10468017, rs493258 and LPL rs12678919 genotypes and haplotype evaluation in patients with age-related macular degeneration","volume":"686","author":"Liutkeviciene","year":"2019","journal-title":"Gene"},{"key":"ref_236","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1038\/eye.2012.276","article-title":"Association of LIPC and advanced age-related macular degeneration","volume":"27","author":"Lee","year":"2013","journal-title":"Eye"},{"key":"ref_237","first-page":"e282","article-title":"The association study of lipid metabolism gene polymorphisms with AMD identifies a protective role for APOE-E2 allele in the wet form in a Northern Spanish population","volume":"98","author":"Olivares","year":"2020","journal-title":"Acta Ophthalmol."},{"key":"ref_238","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1038\/ng.291","article-title":"Common variants at 30 loci contribute to polygenic dyslipidemia","volume":"41","author":"Kathiresan","year":"2009","journal-title":"Nat. Genet."},{"key":"ref_239","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1038\/s41598-021-04269-6","article-title":"Modulated anti-VEGF therapy under the influence of lipid metabolizing proteins in Age related macular degeneration: A pilot study","volume":"12","author":"Sharma","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_240","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/S0021-9150(03)00006-6","article-title":"High density lipoproteins (HDLs) and atherosclerosis; the unanswered questions","volume":"168","author":"Barter","year":"2003","journal-title":"Atherosclerosis"},{"key":"ref_241","first-page":"1306","article-title":"Uptake of cholesterol by the retina occurs primarily via a low density lipoprotein receptor-mediated process","volume":"12","author":"Tserentsoodol","year":"2006","journal-title":"Mol. Vis."},{"key":"ref_242","first-page":"750","article-title":"Cholesterol and age-related macular degeneration: Is there a link?","volume":"137","author":"Klaver","year":"2004","journal-title":"Am. J. Ophthalmol."},{"key":"ref_243","doi-asserted-by":"crossref","first-page":"1","DOI":"10.5551\/jat.13.1","article-title":"ABCA1 and biogenesis of HDL","volume":"13","author":"Yokoyama","year":"2006","journal-title":"J. Atheroscler. Thromb."},{"key":"ref_244","doi-asserted-by":"crossref","first-page":"e45100","DOI":"10.7554\/eLife.45100","article-title":"Impaired ABCA1\/ABCG1-mediated lipid efflux in the mouse retinal pigment epithelium (RPE) leads to retinal degeneration","volume":"8","author":"Storti","year":"2019","journal-title":"eLife"},{"key":"ref_245","doi-asserted-by":"crossref","unstructured":"Peters, F., Ebner, L.J.A., Atac, D., Maggi, J., Berger, W., den Hollander, A.I., and Grimm, C. (2022). Regulation of ABCA1 by AMD-Associated Genetic Variants and Hypoxia in iPSC-RPE. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23063194"},{"key":"ref_246","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.preteyeres.2014.03.002","article-title":"Cholesterol in the retina: The best is yet to come","volume":"41","author":"Pikuleva","year":"2014","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_247","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1007\/s00417-015-3211-z","article-title":"ABCA1 rs1883025 polymorphism and risk of age-related macular degeneration","volume":"254","author":"Wang","year":"2016","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol."},{"key":"ref_248","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1007\/s00109-002-0384-9","article-title":"Lipoprotein lipase: Structure, function, regulation, and role in disease","volume":"80","author":"Mead","year":"2002","journal-title":"J. Mol. Med."},{"key":"ref_249","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1016\/j.ajo.2011.05.016","article-title":"Evaluation of new and established age-related macular degeneration susceptibility genes in the Women\u2019s Health Initiative Sight Exam (WHI-SE) Study","volume":"152","author":"Peter","year":"2011","journal-title":"Am. J. Ophthalmol."},{"key":"ref_250","doi-asserted-by":"crossref","first-page":"4262","DOI":"10.1167\/iovs.11-8542","article-title":"Association of genetic polymorphisms and age-related macular degeneration in Chinese population","volume":"53","author":"Tian","year":"2012","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_251","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.exer.2012.12.005","article-title":"Different impact of high-density lipoprotein-related genetic variants on polypoidal choroidal vasculopathy and neovascular age-related macular degeneration in a Chinese Han population","volume":"108","author":"Zhang","year":"2013","journal-title":"Exp. Eye Res."},{"key":"ref_252","doi-asserted-by":"crossref","unstructured":"Merle, B.M., Maubaret, C., Korobelnik, J.F., Delyfer, M.N., Rougier, M.B., Lambert, J.C., Amouyel, P., Malet, F., Le Goff, M., and Dartigues, J.F. (2013). Association of HDL-related loci with age-related macular degeneration and plasma lutein and zeaxanthin: The Alienor study. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0079848"},{"key":"ref_253","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1016\/j.ajo.2003.09.042","article-title":"Choroidal neovascularization","volume":"137","author":"Grossniklaus","year":"2004","journal-title":"Am. J. Ophthalmol."},{"key":"ref_254","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1038\/6509","article-title":"Fas ligand (CD95 ligand) controls angiogenesis beneath the retina","volume":"5","author":"Kaplan","year":"1999","journal-title":"Nat. Med."},{"key":"ref_255","first-page":"2115","article-title":"Constitutive expression of VEGF, VEGFR-1, and VEGFR-2 in normal eyes","volume":"40","author":"Kim","year":"1999","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_256","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1167\/tvst.5.2.10","article-title":"VEGF and Intraocular Neovascularization: From Discovery to Therapy","volume":"5","author":"Ferrara","year":"2016","journal-title":"Transl. Vis. Sci. Technol."},{"key":"ref_257","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1126\/science.285.5425.245","article-title":"Pigment epithelium-derived factor: A potent inhibitor of angiogenesis","volume":"285","author":"Dawson","year":"1999","journal-title":"Science"},{"key":"ref_258","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1001\/archopht.122.4.598","article-title":"Current concepts in the pathogenesis of age-related macular degeneration","volume":"122","author":"Zarbin","year":"2004","journal-title":"Arch. Ophthalmol."},{"key":"ref_259","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1038\/nrd.2015.17","article-title":"Ten years of anti-vascular endothelial growth factor therapy","volume":"15","author":"Ferrara","year":"2016","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_260","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1016\/j.cell.2019.01.021","article-title":"VEGF in Signaling and Disease: Beyond Discovery and Development","volume":"176","author":"Apte","year":"2019","journal-title":"Cell"},{"key":"ref_261","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.ophtha.2012.07.038","article-title":"Vascular endothelial growth factor a in intraocular vascular disease","volume":"120","author":"Miller","year":"2013","journal-title":"Ophthalmology"},{"key":"ref_262","first-page":"2710","article-title":"Polymorphisms in the VEGFA and VEGFR-2 genes and neovascular age-related macular degeneration","volume":"15","author":"Fang","year":"2009","journal-title":"Mol. Vis."},{"key":"ref_263","doi-asserted-by":"crossref","unstructured":"Vilkeviciute, A., Cebatoriene, D., Kriauciuniene, L., and Liutkeviciene, R. (2022). VEGFA Haplotype and VEGF-A and VEGF-R2 Protein Associations with Exudative Age-Related Macular Degeneration. Cells, 11.","DOI":"10.3390\/cells11060996"},{"key":"ref_264","doi-asserted-by":"crossref","first-page":"818","DOI":"10.21037\/atm-20-2447","article-title":"Interaction of two functional genetic variants LOXL1 rs1048661 and VEGFA rs3025039 on the risk of age-related macular degeneration in Chinese women","volume":"8","author":"Chen","year":"2020","journal-title":"Ann. Transl. Med."},{"key":"ref_265","doi-asserted-by":"crossref","first-page":"1641","DOI":"10.1016\/j.ophtha.2013.01.014","article-title":"Genetic influences on the outcome of anti-vascular endothelial growth factor treatment in neovascular age-related macular degeneration","volume":"120","author":"Abedi","year":"2013","journal-title":"Ophthalmology"},{"key":"ref_266","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1001\/jamaophthalmol.2014.109","article-title":"VEGFA and VEGFR2 gene polymorphisms and response to anti-vascular endothelial growth factor therapy: Comparison of age-related macular degeneration treatments trials (CATT)","volume":"132","author":"Hagstrom","year":"2014","journal-title":"JAMA Ophthalmol."},{"key":"ref_267","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.survophthal.2013.03.009","article-title":"Predictors of anti-VEGF treatment response in neovascular age-related macular degeneration","volume":"59","author":"Finger","year":"2014","journal-title":"Surv. Ophthalmol."},{"key":"ref_268","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1007\/s10792-015-0164-5","article-title":"Clinically detectable drusen domains in fibulin-5-associated age-related macular degeneration (AMD): Drusen subdomains in fibulin-5 AMD","volume":"36","author":"Kucukevcilioglu","year":"2016","journal-title":"Int. Ophthalmol."},{"key":"ref_269","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1016\/j.exer.2006.09.021","article-title":"Fibulin-5 distribution in human eyes: Relevance to age-related macular degeneration","volume":"84","author":"Mullins","year":"2007","journal-title":"Exp. Eye Res."},{"key":"ref_270","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1089\/104454904323145254","article-title":"Fibulin-5 antagonizes vascular endothelial growth factor (VEGF) signaling and angiogenic sprouting by endothelial cells","volume":"23","author":"Albig","year":"2004","journal-title":"DNA Cell Biol."},{"key":"ref_271","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1002\/humu.20344","article-title":"Reduced secretion of fibulin 5 in age-related macular degeneration and cutis laxa","volume":"27","author":"Lotery","year":"2006","journal-title":"Hum. Mutat."},{"key":"ref_272","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1056\/NEJMoa040833","article-title":"Missense variations in the fibulin 5 gene and age-related macular degeneration","volume":"351","author":"Stone","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_273","doi-asserted-by":"crossref","first-page":"1839","DOI":"10.1093\/brain\/awr076","article-title":"Fibulin-5 mutations link inherited neuropathies, age-related macular degeneration and hyperelastic skin","volume":"134","author":"Weger","year":"2011","journal-title":"Brain"},{"key":"ref_274","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.mam.2012.04.005","article-title":"Understanding age-related macular degeneration (AMD): Relationships between the photoreceptor\/retinal pigment epithelium\/Bruch\u2019s membrane\/choriocapillaris complex","volume":"33","author":"Bhutto","year":"2012","journal-title":"Mol. Asp. Med."},{"key":"ref_275","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1017\/S095252389916214X","article-title":"Effects of inhibiting glutamine synthetase and blocking glutamate uptake on b-wave generation in the isolated rat retina","volume":"16","author":"Winkler","year":"1999","journal-title":"Vis. Neurosci."},{"key":"ref_276","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1146\/annurev-genet-021920-092410","article-title":"RAD51 Gene Family Structure and Function","volume":"54","author":"Bonilla","year":"2020","journal-title":"Annu. Rev. Genet."},{"key":"ref_277","doi-asserted-by":"crossref","first-page":"1689","DOI":"10.1016\/j.clinbiochem.2013.07.002","article-title":"RAD51 gene is associated with advanced age-related macular degeneration in Chinese population","volume":"46","author":"Zhou","year":"2013","journal-title":"Clin. Biochem."},{"key":"ref_278","doi-asserted-by":"crossref","first-page":"9627","DOI":"10.1007\/s11357-014-9627-2","article-title":"In-depth analyses unveil the association and possible functional involvement of novel RAD51B polymorphisms in age-related macular degeneration","volume":"36","author":"Chu","year":"2014","journal-title":"Age"},{"key":"ref_279","first-page":"181","article-title":"Serum Levels of ARMS2, COL8A1, RAD51B, and VEGF and their Correlations in Age-related Macular Degeneration","volume":"18","author":"Battu","year":"2021","journal-title":"Curr. Neurovasc. Res."},{"key":"ref_280","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1002\/1439-7633(20010105)2:1<20::AID-CBIC20>3.0.CO;2-X","article-title":"Molecular mechanisms of death-receptor-mediated apoptosis","volume":"2","author":"Sartorius","year":"2001","journal-title":"Chembiochem"},{"key":"ref_281","doi-asserted-by":"crossref","unstructured":"Mori, K., Ishikawa, K., Fukuda, Y., Ji, R., Wada, I., Kubo, Y., Akiyama, M., Notomi, S., Murakami, Y., and Nakao, S. (2022). TNFRSF10A downregulation induces retinal pigment epithelium degeneration during the pathogenesis of age-related macular degeneration and central serous chorioretinopathy. Hum. Mol. Genet., ddac020.","DOI":"10.1093\/hmg\/ddac020"},{"key":"ref_282","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1038\/ng.938","article-title":"Genome-wide association study identifies two susceptibility loci for exudative age-related macular degeneration in the Japanese population","volume":"43","author":"Arakawa","year":"2011","journal-title":"Nat. Genet."},{"key":"ref_283","doi-asserted-by":"crossref","first-page":"8199","DOI":"10.1167\/iovs.13-12867","article-title":"TNFRSF10A-LOC389641 rs13278062 but not REST-C4orf14-POLR2B-IGFBP7 rs1713985 was found associated with age-related macular degeneration in a Chinese population","volume":"54","author":"Sun","year":"2013","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_284","doi-asserted-by":"crossref","first-page":"9256","DOI":"10.1073\/pnas.0603485103","article-title":"Synergic effect of polymorphisms in ERCC6 5\u2019 flanking region and complement factor H on age-related macular degeneration predisposition","volume":"103","author":"Tuo","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_285","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1016\/0092-8674(92)90390-X","article-title":"ERCC6, a member of a subfamily of putative helicases, is involved in Cockayne\u2019s syndrome and preferential repair of active genes","volume":"71","author":"Troelstra","year":"1992","journal-title":"Cell"},{"key":"ref_286","doi-asserted-by":"crossref","unstructured":"Baas, D.C., Despriet, D.D., Gorgels, T.G., Bergeron-Sawitzke, J., Uitterlinden, A.G., Hofman, A., van Duijn, C.M., Merriam, J.E., Smith, R.T., and Barile, G.R. (2010). The ERCC6 gene and age-related macular degeneration. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0013786"},{"key":"ref_287","doi-asserted-by":"crossref","first-page":"13378","DOI":"10.3390\/ijms131013378","article-title":"Genetic variability in DNA repair proteins in age-related macular degeneration","volume":"13","author":"Blasiak","year":"2012","journal-title":"Int. J. Mol. Sci."},{"key":"ref_288","doi-asserted-by":"crossref","first-page":"3129","DOI":"10.1167\/iovs.10-6735","article-title":"Copy number variations in candidate genes in neovascular age-related macular degeneration","volume":"52","author":"Liu","year":"2011","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_289","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1016\/S0002-9394(01)01214-4","article-title":"Age-related maculopathy: An expanded genome-wide scan with evidence of susceptibility loci within the 1q31 and 17q25 regions","volume":"132","author":"Weeks","year":"2001","journal-title":"Am. J. Ophthalmol."},{"key":"ref_290","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1086\/422476","article-title":"Age-related maculopathy: A genomewide scan with continued evidence of susceptibility loci within the 1q31, 10q26, and 17q25 regions","volume":"75","author":"Weeks","year":"2004","journal-title":"Am. J. Hum. Genet."},{"key":"ref_291","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1086\/380912","article-title":"Dissection of genomewide-scan data in extended families reveals a major locus and oligogenic susceptibility for age-related macular degeneration","volume":"74","author":"Iyengar","year":"2004","journal-title":"Am. J. Hum. Genet."},{"key":"ref_292","first-page":"57","article-title":"Linkage analysis for age-related macular degeneration supports a gene on chromosome 10q26","volume":"10","author":"Kenealy","year":"2004","journal-title":"Mol. Vis."},{"key":"ref_293","doi-asserted-by":"crossref","first-page":"2257","DOI":"10.1093\/hmg\/ddi230","article-title":"Meta-analysis of genome scans of age-related macular degeneration","volume":"14","author":"Fisher","year":"2005","journal-title":"Hum. Mol. Genet."},{"key":"ref_294","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1126\/science.1133811","article-title":"A variant of the HTRA1 gene increases susceptibility to age-related macular degeneration","volume":"314","author":"Yang","year":"2006","journal-title":"Science"},{"key":"ref_295","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.tig.2007.03.001","article-title":"The challenge of modeling macular degeneration in mice","volume":"23","author":"Marmorstein","year":"2007","journal-title":"Trends Genet."},{"key":"ref_296","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1001\/jamaophthalmol.2013.713","article-title":"Risk alleles in CFH and ARMS2 and the long-term natural history of age-related macular degeneration: The Beaver Dam Eye Study","volume":"131","author":"Klein","year":"2013","journal-title":"JAMA Ophthalmol."},{"key":"ref_297","doi-asserted-by":"crossref","unstructured":"Wyatt, M.K., Tsai, J.Y., Mishra, S., Campos, M., Jaworski, C., Fariss, R.N., Bernstein, S.L., and Wistow, G. (2013). Interaction of complement factor h and fibulin3 in age-related macular degeneration. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0068088"},{"key":"ref_298","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1086\/444437","article-title":"Susceptibility genes for age-related maculopathy on chromosome 10q26","volume":"77","author":"Jakobsdottir","year":"2005","journal-title":"Am. J. Hum. Genet."},{"key":"ref_299","doi-asserted-by":"crossref","first-page":"3227","DOI":"10.1093\/hmg\/ddi353","article-title":"Hypothetical LOC387715 is a second major susceptibility gene for age-related macular degeneration, contributing independently of complement factor H to disease risk","volume":"14","author":"Rivera","year":"2005","journal-title":"Hum. Mol. Genet."},{"key":"ref_300","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1126\/science.1133807","article-title":"HTRA1 promoter polymorphism in wet age-related macular degeneration","volume":"314","author":"Dewan","year":"2006","journal-title":"Science"},{"key":"ref_301","doi-asserted-by":"crossref","first-page":"3206","DOI":"10.1093\/hmg\/ddl396","article-title":"CFH, ELOVL4, PLEKHA1 and LOC387715 genes and susceptibility to age-related maculopathy: AREDS and CHS cohorts and meta-analyses","volume":"15","author":"Conley","year":"2006","journal-title":"Hum. Mol. Genet."},{"key":"ref_302","doi-asserted-by":"crossref","first-page":"16227","DOI":"10.1073\/pnas.0703933104","article-title":"A variant of mitochondrial protein LOC387715\/ARMS2, not HTRA1, is strongly associated with age-related macular degeneration","volume":"104","author":"Kanda","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_303","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.2147\/OPTH.S11627","article-title":"Update on the role of genetics in the onset of age-related macular degeneration","volume":"5","author":"Francis","year":"2011","journal-title":"Clin. Ophthalmol."},{"key":"ref_304","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1111\/aos.12799","article-title":"The genetic variant rs4073 AT of the Interleukin-8 promoter region is associated with the earlier onset of exudative age-related macular degeneration","volume":"93","author":"Hautamaki","year":"2015","journal-title":"Acta Ophthalmol."},{"key":"ref_305","doi-asserted-by":"crossref","unstructured":"Woo, S.J., Ahn, J., Morrison, M.A., Ahn, S.Y., Lee, J., Kim, K.W., DeAngelis, M.M., and Park, K.H. (2015). Analysis of Genetic and Environmental Risk Factors and Their Interactions in Korean Patients with Age-Related Macular Degeneration. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0132771"},{"key":"ref_306","first-page":"4","article-title":"The interplay of oxidative stress and ARMS2-HTRA1 genetic risk in neovascular AMD","volume":"5","author":"Lu","year":"2021","journal-title":"Vessel. Plus"},{"key":"ref_307","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.ophtha.2011.07.056","article-title":"Risk alleles in CFH and ARMS2 are independently associated with systemic complement activation in age-related macular degeneration","volume":"119","author":"Smailhodzic","year":"2012","journal-title":"Ophthalmology"},{"key":"ref_308","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1038\/ng.170","article-title":"Age-related macular degeneration is associated with an unstable ARMS2 (LOC387715) mRNA","volume":"40","author":"Fritsche","year":"2008","journal-title":"Nat. Genet."},{"key":"ref_309","doi-asserted-by":"crossref","first-page":"3084","DOI":"10.1167\/iovs.08-3240","article-title":"Localization of age-related macular degeneration-associated ARMS2 in cytosol, not mitochondria","volume":"50","author":"Wang","year":"2009","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_310","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1167\/iovs.09-3850","article-title":"ARMS2 is a constituent of the extracellular matrix providing a link between familial and sporadic age-related macular degenerations","volume":"51","author":"Kortvely","year":"2010","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_311","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s12974-016-0776-3","article-title":"Age-related macular degeneration associated polymorphism rs10490924 in ARMS2 results in deficiency of a complement activator","volume":"14","author":"Micklisch","year":"2017","journal-title":"J. Neuroinflam."},{"key":"ref_312","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1042\/BST0350669","article-title":"HtrA1: A novel regulator of physiological and pathological matrix mineralization?","volume":"35","author":"Canfield","year":"2007","journal-title":"Biochem. Soc. Trans."},{"key":"ref_313","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/j.immuni.2020.07.021","article-title":"The 10q26 Risk Haplotype of Age-Related Macular Degeneration Aggravates Subretinal Inflammation by Impairing Monocyte Elimination","volume":"53","author":"Beguier","year":"2020","journal-title":"Immunity"},{"key":"ref_314","doi-asserted-by":"crossref","first-page":"e2103617118","DOI":"10.1073\/pnas.2103617118","article-title":"Chromosome 10q26-driven age-related macular degeneration is associated with reduced levels of HTRA1 in human retinal pigment epithelium","volume":"118","author":"Williams","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_315","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1586\/17469899.2.3.443","article-title":"Genetic markers and biomarkers for age-related macular degeneration","volume":"2","author":"Ross","year":"2007","journal-title":"Expert Rev. Ophthalmol."},{"key":"ref_316","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1038\/ejhg.2009.23","article-title":"Multilocus analysis of age-related macular degeneration","volume":"17","author":"Gold","year":"2009","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_317","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/s40246-019-0197-3","article-title":"Association of HTRA1 and ARMS2 gene polymorphisms with response to intravitreal ranibizumab among neovascular age-related macular degenerative subjects","volume":"13","author":"Mohamad","year":"2019","journal-title":"Hum. Genom."},{"key":"ref_318","doi-asserted-by":"crossref","first-page":"2735","DOI":"10.1007\/s10792-020-01460-y","article-title":"Association of CRP levels with ARMS2 and CFH variants in age-related macular degeneration","volume":"40","author":"Shijo","year":"2020","journal-title":"Int. Ophthalmol."},{"key":"ref_319","first-page":"1987","article-title":"A pharmacogenetics study to predict outcome in patients receiving anti-VEGF therapy in age related macular degeneration","volume":"7","author":"Kitchens","year":"2013","journal-title":"Clin. Ophthalmol."},{"key":"ref_320","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1007\/s10384-019-00683-6","article-title":"Association of an age-related maculopathy susceptibility 2 gene variant with the 12-month outcomes of intravitreal aflibercept combined with photodynamic therapy for polypoidal choroidal vasculopathy","volume":"63","author":"Nakai","year":"2019","journal-title":"Jpn J. Ophthalmol."},{"key":"ref_321","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1159\/000508738","article-title":"Meta-Analysis of the Pharmacogenetics of ARMS2 A69S Polymorphism and the Response to Advanced Age-Related Macular Degeneration","volume":"64","author":"Zhang","year":"2021","journal-title":"Ophthalmic Res."},{"key":"ref_322","doi-asserted-by":"crossref","first-page":"821918","DOI":"10.1155\/2015\/821918","article-title":"Joint Effect of CFH and ARMS2\/HTRA1 Polymorphisms on Neovascular Age-Related Macular Degeneration in Chinese Population","volume":"2015","author":"Fang","year":"2015","journal-title":"J. Ophthalmol."},{"key":"ref_323","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1016\/j.ophtha.2009.10.007","article-title":"The prevalence of age-related macular degeneration in Asians: A systematic review and meta-analysis","volume":"117","author":"Kawasaki","year":"2010","journal-title":"Ophthalmology"},{"key":"ref_324","first-page":"3436","article-title":"Association of c.*372_815del443ins54 Polymorphism in the ARMS2 (LOC387715) Gene With Neovascular Age-Related Macular Degeneration (AMD) and Polypoidal Choroidal Vasculopathy (PCV) in a Japanese Population","volume":"50","author":"Yasuma","year":"2009","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_325","doi-asserted-by":"crossref","first-page":"2295","DOI":"10.1016\/j.ophtha.2015.07.032","article-title":"MMP20 and ARMS2\/HTRA1 Are Associated with Neovascular Lesion Size in Age-Related Macular Degeneration","volume":"122","author":"Yamashiro","year":"2015","journal-title":"Ophthalmology"},{"key":"ref_326","doi-asserted-by":"crossref","unstructured":"Yang, Z., Tong, Z., Chen, Y., Zeng, J., Lu, F., Sun, X., Zhao, C., Wang, K., Davey, L., and Chen, H. (2010). Genetic and functional dissection of HTRA1 and LOC387715 in age-related macular degeneration. PLoS Genet., 6.","DOI":"10.1371\/journal.pgen.1000836"},{"key":"ref_327","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1016\/j.ajo.2009.07.002","article-title":"Comprehensive analysis of complement factor H and LOC387715\/ARMS2\/HTRA1 variants with respect to phenotype in advanced age-related macular degeneration","volume":"148","author":"Andreoli","year":"2009","journal-title":"Am. J. Ophthalmol."},{"key":"ref_328","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1016\/j.ophtha.2007.10.032","article-title":"Alleles in the HtrA serine peptidase 1 gene alter the risk of neovascular age-related macular degeneration","volume":"115","author":"Deangelis","year":"2008","journal-title":"Ophthalmology"},{"key":"ref_329","doi-asserted-by":"crossref","first-page":"2357","DOI":"10.1167\/iovs.07-1520","article-title":"HTRA1 variants in exudative age-related macular degeneration and interactions with smoking and CFH","volume":"49","author":"Tam","year":"2008","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_330","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1093\/jmcb\/mjx024","article-title":"ER stress-induced aggresome trafficking of HtrA1 protects against proteotoxicity","volume":"9","author":"Gerhardt","year":"2017","journal-title":"J. Mol. Cell Biol."},{"key":"ref_331","doi-asserted-by":"crossref","first-page":"1976","DOI":"10.1128\/MCB.01283-12","article-title":"Age-related macular degeneration-associated silent polymorphisms in HtrA1 impair its ability to antagonize insulin-like growth factor 1","volume":"33","author":"Jacobo","year":"2013","journal-title":"Mol. Cell Biol."},{"key":"ref_332","doi-asserted-by":"crossref","first-page":"056013","DOI":"10.1088\/1741-2552\/aa7d5c","article-title":"The relationship between retinal damage and current intensity in a pre-clinical suprachoroidal-transretinal stimulation model using a laser-formed microporous electrode","volume":"14","author":"Kanda","year":"2017","journal-title":"J. Neural. Eng."},{"key":"ref_333","first-page":"13","article-title":"Age-related macular degeneration","volume":"9","author":"Wang","year":"2010","journal-title":"Discov. Med."},{"key":"ref_334","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.exer.2013.04.019","article-title":"Variants at chromosome 10q26 locus and the expression of HTRA1 in the retina","volume":"112","author":"Wang","year":"2013","journal-title":"Exp. Eye Res."},{"key":"ref_335","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1093\/hmg\/ddr020","article-title":"Risk- and non-risk-associated variants at the 10q26 AMD locus influence ARMS2 mRNA expression but exclude pathogenic effects due to protein deficiency","volume":"20","author":"Friedrich","year":"2011","journal-title":"Hum. Mol. Genet."},{"key":"ref_336","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1016\/j.ophtha.2020.08.031","article-title":"Predicting Progression to Advanced Age-Related Macular Degeneration from Clinical, Genetic, and Lifestyle Factors Using Machine Learning","volume":"128","author":"Ajana","year":"2021","journal-title":"Ophthalmology"},{"key":"ref_337","first-page":"75","article-title":"The Use of Genetic Testing in the Management of Patients With Age-Related Macular Degeneration:American Society of Retina Specialists Genetics Task Force Special Report","volume":"1","author":"Csaky","year":"2017","journal-title":"J. Vitr. Dis."},{"key":"ref_338","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1136\/bjophthalmol-2020-318452","article-title":"Treatments for dry age-related macular degeneration: Therapeutic avenues, clinical trials and future directions","volume":"106","author":"Georgiou","year":"2022","journal-title":"Br. J. Ophthalmol."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/7\/1233\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:48:52Z","timestamp":1760140132000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/7\/1233"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,12]]},"references-count":338,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2022,7]]}},"alternative-id":["genes13071233"],"URL":"https:\/\/doi.org\/10.3390\/genes13071233","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,12]]}}}