{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T20:48:13Z","timestamp":1790801293587,"version":"4.1.0"},"reference-count":62,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2021,11,3]],"date-time":"2021-11-03T00:00:00Z","timestamp":1635897600000},"content-version":"vor","delay-in-days":440,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,8,20]],"date-time":"2020-08-20T00:00:00Z","timestamp":1597881600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,8,20]],"date-time":"2020-08-20T00:00:00Z","timestamp":1597881600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"name":"Newcastle upon Tyne Hospitals NHS Charity","award":["BH182022"],"award-info":[{"award-number":["BH182022"]}]},{"DOI":"10.13039\/501100000774","name":"Newcastle University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000774","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000268","name":"BBSRC","doi-asserted-by":"publisher","award":["BB\/R013942\/1"],"award-info":[{"award-number":["BB\/R013942\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Macular Society UK"},{"DOI":"10.13039\/501100000774","name":"Newcastle University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000774","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/R013942\/1"],"award-info":[{"award-number":["BB\/R013942\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Age-related macular degeneration (AMD) is a multifactorial disease, which is characterized by loss of central vision, affecting one in three people by the age of 75. The Y402H polymorphism in the complement factor H (CFH) gene significantly increases the risk of AMD. We show that Y402H-AMD-patient-specific retinal pigment epithelium (RPE) cells are characterized by a significant reduction in the number of melanosomes, an increased number of swollen lysosome-like-vesicles with fragile membranes, Cathepsin D leakage into drusen-like deposits and reduced lysosomal function. The turnover of C3 is increased significantly in high-risk RPE cells, resulting in higher internalization and deposition of the terminal complement complex C5b-9 at the lysosomes. Inhibition of C3 processing via the compstatin analogue Cp40 reverses the disease phenotypes by relieving the lysosomes of their overburden and restoring their function. These findings suggest that modulation of the complement system represents a useful therapeutic approach for AMD patients associated with complement dysregulation.<\/jats:p>\n               <jats:sec>\n                  <jats:title\/>\n                  <jats:p>Significance statement Currently, there is no treatment for dry age-related macular degeneration (AMD), which comprises the majority of AMD pathology. In a collaborative effort, this study describes a novel link between uncontrolled complement activation and autophagy-lysosome axis, which is caused by increased deposition of the terminal attack complex C5b-9 at the lysosomes, leading to their overburdening and malfunction. Using an inhibitor of C3 processing, Cp40, this study shows that all the disease phenotypes are reversed, relieving the lysosomes of their overburden and restoring their function. These findings suggest that modulation of the complement system represents a useful therapeutic approach for AMD patients associated with complement dysregulation.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1002\/sctm.20-0211","type":"journal-article","created":{"date-parts":[[2020,8,27]],"date-time":"2020-08-27T19:48:11Z","timestamp":1598557691000},"page":"1585-1603","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["Complement modulation reverses pathology in Y402H-retinal pigment epithelium cell model of age-related macular degeneration by restoring lysosomal function"],"prefix":"10.1093","volume":"9","author":[{"given":"Edvinas","family":"Cerniauskas","sequence":"first","affiliation":[{"name":"1 Biosciences Institute, Faculty of Medical Sciences Newcastle University, Newcastle upon Tyne, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marzena","family":"Kurzawa-Akanbi","sequence":"additional","affiliation":[{"name":"1 Biosciences Institute, Faculty of Medical Sciences Newcastle University, Newcastle upon Tyne, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long","family":"Xie","sequence":"additional","affiliation":[{"name":"2 Clinical & Translational Research Institute, Faculty of Medical Sciences Newcastle University, Newcastle upon Tyne, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dean","family":"Hallam","sequence":"additional","affiliation":[{"name":"1 Biosciences Institute, Faculty of Medical Sciences Newcastle University, Newcastle upon Tyne, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Moya-Molina","sequence":"additional","affiliation":[{"name":"1 Biosciences Institute, Faculty of Medical Sciences Newcastle University, Newcastle upon Tyne, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn","family":"White","sequence":"additional","affiliation":[{"name":"1 Biosciences Institute, Faculty of Medical Sciences Newcastle University, Newcastle upon Tyne, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Steel","sequence":"additional","affiliation":[{"name":"1 Biosciences Institute, Faculty of Medical Sciences Newcastle University, Newcastle upon Tyne, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Doherty","sequence":"additional","affiliation":[{"name":"3 University of the Highlands and Islands, Inverness, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phil","family":"Whitfield","sequence":"additional","affiliation":[{"name":"3 University of the Highlands and Islands, Inverness, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jumana","family":"Al-Aama","sequence":"additional","affiliation":[{"name":"4 Department of Genetic Medicine and Princess Al-Jawhara Center of Excellence in Research of Hereditary Disorders, Faculty of Medicine King Abdulaziz University, Jeddah, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lyle","family":"Armstrong","sequence":"additional","affiliation":[{"name":"1 Biosciences Institute, Faculty of Medical Sciences Newcastle University, Newcastle upon Tyne, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Kavanagh","sequence":"additional","affiliation":[{"name":"2 Clinical & Translational Research Institute, Faculty of Medical Sciences Newcastle University, Newcastle upon Tyne, UK"},{"name":"5 National Renal Complement Therapeutics Centre, Royal Victoria Infirmary, Newcastle upon Tyne, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John D.","family":"Lambris","sequence":"additional","affiliation":[{"name":"6 Department of Pathology and Laboratory Medicine University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viktor I.","family":"Korolchuk","sequence":"additional","affiliation":[{"name":"1 Biosciences Institute, Faculty of Medical Sciences Newcastle University, Newcastle upon Tyne, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Harris","sequence":"additional","affiliation":[{"name":"2 Clinical & Translational Research Institute, Faculty of Medical Sciences Newcastle University, Newcastle upon Tyne, UK"},{"name":"5 National Renal Complement Therapeutics Centre, Royal Victoria Infirmary, Newcastle upon Tyne, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Majlinda","family":"Lako","sequence":"additional","affiliation":[{"name":"1 Biosciences Institute, Faculty of Medical Sciences Newcastle University, Newcastle upon Tyne, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,8,20]]},"reference":[{"key":"2022022809442494800_sct312794-bib-0001","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/S1534-5807(04)00099-1","article-title":"Development by self-digestion: molecular mechanisms and biological functions of autophagy","volume":"6","author":"Levine","year":"2004","journal-title":"Dev Cell"},{"key":"2022022809442494800_sct312794-bib-0002","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/S0014-4835(86)80023-9","article-title":"Influence of early photoreceptor degeneration on lipofuscin in the retinal pigment epithelium","volume":"43","author":"Katz","year":"1986","journal-title":"Exp Eye Res"},{"key":"2022022809442494800_sct312794-bib-0003","volume-title":"Retinal Degenerative Diseases (Advances in Experimental Medicine and Biology (723))","author":"Lakkaraju","year":"2012"},{"key":"2022022809442494800_sct312794-bib-0004","first-page":"815","article-title":"The effects of hibernation on cone visual cells in the ground squirrel","volume":"16","author":"Reme","year":"1977","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"2022022809442494800_sct312794-bib-0005","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.4161\/auto.5.8.10087","article-title":"Using LC3 to monitor autophagy flux in the retinal pigment epithelium","volume":"5","author":"Wang","year":"2009","journal-title":"Autophagy"},{"key":"2022022809442494800_sct312794-bib-0006","doi-asserted-by":"crossref","first-page":"3245","DOI":"10.1039\/c2cs15328a","article-title":"Autophagy-regulating small molecules and their therapeutic applications","volume":"41","author":"Baek","year":"2012","journal-title":"Chem Soc Rev"},{"key":"2022022809442494800_sct312794-bib-0007","doi-asserted-by":"crossref","first-page":"1692","DOI":"10.1038\/eye.2010.122","article-title":"Causes of blind and partial sight certifications in England and Wales: April 2007-March 2008","volume":"24","author":"Bunce","year":"2010","journal-title":"Eye"},{"issue":"11","key":"2022022809442494800_sct312794-bib-0008","first-page":"1621","article-title":"Potential public health impact of age-related eye disease study","volume":"121","author":"Manuscript","year":"2006","journal-title":"Arch Ophthalmol"},{"key":"2022022809442494800_sct312794-bib-0009","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1136\/bjo.87.3.312","article-title":"How big is the burden of visual loss caused by age related macular degeneration in the United Kingdom?","volume":"87","author":"Owen","year":"2003","journal-title":"Br J Ophthalmol"},{"key":"2022022809442494800_sct312794-bib-0010","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1136\/bjo.82.7.743","article-title":"Bilateral involvement by age related maculopathy lesions in a population","volume":"82","author":"Wang","year":"1998","journal-title":"Br J Ophthalmol"},{"key":"2022022809442494800_sct312794-bib-0011","first-page":"353","article-title":"Age-related macular degeneration (AMD): pathogenesis and therapy","volume":"58","author":"Nowak","year":"2006","journal-title":"Pharmacol Rep"},{"key":"2022022809442494800_sct312794-bib-0012","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1097\/00006982-200510000-00001","article-title":"Enhanced efficacy associated with early treatment of neovascular age-related macular degeneration with pegaptanib sodium: an exploratory analysis","volume":"25","author":"Gonzales","year":"2005","journal-title":"Retina"},{"issue":"16","key":"2022022809442494800_sct312794-bib-0013","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3310\/hta12160","article-title":"Ranibizumab and pegaptanib for the treatment of age-related macular degeneration: a systematic review and economic evaluation","volume":"12","author":"Colquitt","year":"2008","journal-title":"Health Technol Assess"},{"key":"2022022809442494800_sct312794-bib-0014","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.ophtha.2008.10.018","article-title":"Ranibizumab versus verteporfin photodynamic therapy for neovascular age-related macular degeneration: two-year results of the ANCHOR study","volume":"116","author":"Brown","year":"2006","journal-title":"Ophthalmology"},{"key":"2022022809442494800_sct312794-bib-0015"},{"key":"2022022809442494800_sct312794-bib-0016","doi-asserted-by":"crossref","first-page":"1989","DOI":"10.4161\/auto.36184","article-title":"Dysregulated autophagy in the RPE is associated with increased susceptibility to oxidative stress and AMD","volume":"10","author":"Mitter","year":"2014","journal-title":"Autophagy"},{"issue":"1","key":"2022022809442494800_sct312794-bib-0017","doi-asserted-by":"crossref","first-page":"e4160","DOI":"10.1371\/journal.pone.0004160","article-title":"Autophagy and Exosomes in the Aged Retinal Pigment Epithelium: Possible Relevance to Drusen Formation and Age-Related Macular Degeneration","volume":"4","author":"Wang","year":"2009","journal-title":"PLoS ONE"},{"key":"2022022809442494800_sct312794-bib-0018","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1096\/fj.03-0289fje","article-title":"Inhibition of the ATP-driven proton pump in RPE lysosomes by the major lipofuscin fluorophore A2-E may contribute to the pathogenesis of age-related macular degeneration","volume":"18","author":"Bergmann","year":"2004","journal-title":"FASEB J"},{"key":"2022022809442494800_sct312794-bib-0019","doi-asserted-by":"crossref","first-page":"7506","DOI":"10.1074\/jbc.M112.439935","article-title":"Autophagy protects the retina from light-induced degeneration","volume":"288","author":"Chen","year":"2013","journal-title":"J Biol Chem"},{"issue":"6","key":"2022022809442494800_sct312794-bib-0020","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1016\/j.ajhg.2015.04.006","article-title":"Biallelic Mutations in the Autophagy Regulator DRAM2 Cause Retinal Dystrophy with Early Macular Involvement","volume":"96","author":"El-Asrag","year":"2015","journal-title":"The American Journal of Human Genetics"},{"key":"2022022809442494800_sct312794-bib-0021","doi-asserted-by":"crossref","first-page":"2305","DOI":"10.1002\/stem.2708","article-title":"An induced pluripotent stem cell patient specific model of complement factor H (Y402H) polymorphism displays characteristic features of age-related macular degeneration and indicates a beneficial role for UV light exposure","volume":"35","author":"Hallam","year":"2017","journal-title":"Stem Cells"},{"key":"2022022809442494800_sct312794-bib-0022","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.immuni.2016.08.003","article-title":"Complement regulation of metabolism and basic cellular processes","volume":"45","author":"Hess","year":"2017","journal-title":"Immunity"},{"issue":"1","key":"2022022809442494800_sct312794-bib-0023","article-title":"Blockage of the lysosome-dependent autophagic pathway contributes to complement membrane attack complex-induced podocyte injury in idiopathic membranous nephropathy","volume":"7","author":"Liu","year":"2017","journal-title":"Scientific Reports"},{"key":"2022022809442494800_sct312794-bib-0024","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.cmet.2018.09.009","article-title":"Complement component C3 is highly expressed in human pancreatic islets and prevents \u03b2 cell death via ATG16L1 interaction and autophagy regulation","volume":"29","author":"King","year":"2019","journal-title":"Cell Metab"},{"key":"2022022809442494800_sct312794-bib-0025","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1016\/j.immuni.2013.10.018","article-title":"Intracellular complement activation sustains T cell homeostasis and mediates effector differentiation","volume":"39","author":"Liszewski","year":"2013","journal-title":"Immunity"},{"key":"2022022809442494800_sct312794-bib-0026","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1038\/nrm2258","article-title":"Melanosomes\u2014dark organelles enlighten endosomal membrane transport","volume":"8","author":"Raposo","year":"2007","journal-title":"Nat Rev Mol Cell Biol"},{"key":"2022022809442494800_sct312794-bib-0027","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1016\/j.exer.2011.10.011","article-title":"A novel melano-lysosome in the retinal epithelium of rhesus monkeys","volume":"93","author":"Gouras","year":"2011","journal-title":"Exp Eye Res"},{"key":"2022022809442494800_sct312794-bib-0028","doi-asserted-by":"crossref","first-page":"1","DOI":"10.12703\/P6-52","article-title":"mTOR and lysosome regulation","volume":"6","author":"Puertollano","year":"2014","journal-title":"F1000Prime Rep"},{"key":"2022022809442494800_sct312794-bib-0029","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/j.oret.2017.08.015","article-title":"Treatment of geographic atrophy with intravitreal sirolimus: the age-related eye disease study 2 ancillary study","volume":"2","author":"Gensler","year":"2018","journal-title":"Ophthalmol Retina"},{"key":"2022022809442494800_sct312794-bib-0030","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.1016\/S0002-9440(10)64427-6","article-title":"Progressive age-related changes similar to age-related macular degeneration in a transgenic mouse model","volume":"161","author":"Rakoczy","year":"2002","journal-title":"Am J Pathol"},{"key":"2022022809442494800_sct312794-bib-0031","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1006\/exer.1999.0700","article-title":"Distribution of cathepsin D in human eyes with or without age-related maculpathy","volume":"69","author":"Ophthalmology","year":"1999","journal-title":"Exp Eye Res"},{"key":"2022022809442494800_sct312794-bib-0032","doi-asserted-by":"crossref","first-page":"18277","DOI":"10.1073\/pnas.1109703108","article-title":"Cell culture model that mimics drusen formation and triggers complement activation associated with age-related macular degeneration","volume":"108","author":"Johnson","year":"2011","journal-title":"Proc Natl Acad Sci USA"},{"key":"2022022809442494800_sct312794-bib-0033"},{"key":"2022022809442494800_sct312794-bib-0034","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/S0940-9602(11)80384-5","article-title":"Localization of lysosomal enzymes in the retina and retinal pigment epithelium of RCS rats","volume":"176","author":"El-Hifnawi","year":"1994","journal-title":"Ann Anat"},{"key":"2022022809442494800_sct312794-bib-0035","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1080\/15548627.2018.1505155","article-title":"Galectins control MTOR and AMPK in response to lysosomal damage to induce autophagy","volume":"15","author":"Jia","year":"2019","journal-title":"Autophagy"},{"key":"2022022809442494800_sct312794-bib-0036","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2017\/5306790","article-title":"Depletion of the third complement component ameliorates age-dependent oxidative stress and positively modulates autophagic activity in aged retinas in a mouse model","volume":"2017","author":"Rogi\u0144ska","year":"2017","journal-title":"Oxid Med Cell Longev"},{"key":"2022022809442494800_sct312794-bib-0037","first-page":"2782","article-title":"Regulation of RPE intercellular junction integrity and function by hepatocyte growth factor","volume":"43","author":"Jin","year":"2002","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"2022022809442494800_sct312794-bib-0038","doi-asserted-by":"crossref","first-page":"3382","DOI":"10.4049\/jimmunol.1500937","article-title":"Retinal pigment epithelial cells mitigate the effects of complement attack by endocytosis of C5b-9","volume":"195","author":"Georgiannakis","year":"2015","journal-title":"J Immunol"},{"key":"2022022809442494800_sct312794-bib-0039","doi-asserted-by":"crossref","first-page":"6153","DOI":"10.1021\/acs.jmedchem.8b00560","article-title":"New analogs of the complement C3 inhibitor compstatin with increased solubility and improved pharmacokinetic profile","volume":"61","author":"Berger","year":"2018","journal-title":"J Med Chem"},{"issue":"4","key":"2022022809442494800_sct312794-bib-0040","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1016\/j.imbio.2014.10.026","article-title":"Therapeutic C3 inhibitor Cp40 abrogates complement activation induced by modern hemodialysis filters","volume":"220","author":"Reis","year":"2015","journal-title":"Immunobiology"},{"issue":"21","key":"2022022809442494800_sct312794-bib-0041","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1182\/blood.V122.21.1239.1239","article-title":"Preclinical development and in vivo evaluation of next-generation compstatin analogs with improved systemic profiles: a novel option for the treatment of paroxysmal nocturnal hemoglobinuria","volume":"122","author":"Ricklin","year":"2013","journal-title":"Blood"},{"key":"2022022809442494800_sct312794-bib-0042","doi-asserted-by":"crossref","first-page":"1342","DOI":"10.1016\/j.stemcr.2019.04.012","article-title":"Human iPSC-derived retinal pigment epithelium: a model system for prioritizing and functionally characterizing causal variants at AMD risk loci","volume":"12","author":"Smith","year":"2019","journal-title":"Stem Cell Reports"},{"key":"2022022809442494800_sct312794-bib-0043","doi-asserted-by":"crossref","first-page":"3445","DOI":"10.1093\/hmg\/ddu053","article-title":"Validation of genome-wide association study (GWAS)-identified disease risk alleles with patient-specific stem cell lines","volume":"23","author":"Yang","year":"2014","journal-title":"Hum Mol Genet"},{"key":"2022022809442494800_sct312794-bib-0044","doi-asserted-by":"crossref","first-page":"191","DOI":"10.3389\/fnagi.2014.00191","article-title":"The generation of induced pluripotent stem cells for macular degeneration as a drug screening platform: identification of curcumin as a protective agent for retinal pigment epithelial cells against oxidative stress","volume":"6","author":"Chang","year":"2014","journal-title":"Front Aging Neurosci"},{"issue":"1","key":"2022022809442494800_sct312794-bib-0045","doi-asserted-by":"crossref","DOI":"10.1186\/s12967-016-1101-8","article-title":"Repressed SIRT1\/PGC-1\u03b1 pathway and mitochondrial disintegration in iPSC-derived RPE disease model of age-related macular degeneration","volume":"14","author":"Golestaneh","year":"2016","journal-title":"Journal of Translational Medicine"},{"issue":"5","key":"2022022809442494800_sct312794-bib-0046","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/j.stem.2016.12.015","article-title":"Nicotinamide Ameliorates Disease Phenotypes in a Human iPSC Model of Age-Related Macular Degeneration","volume":"20","author":"Saini","year":"2017","journal-title":"Cell Stem Cell"},{"key":"2022022809442494800_sct312794-bib-0047","doi-asserted-by":"crossref","first-page":"e69563","DOI":"10.1371\/journal.pone.0069563","article-title":"Autophagy activation clears ELAVL1\/HuR-mediated accumulation of SQSTM1\/p62 during proteasomal inhibition in human retinal pigment epithelial cells","volume":"8","author":"Viiri","year":"2013","journal-title":"PLoS One"},{"key":"2022022809442494800_sct312794-bib-0048","doi-asserted-by":"crossref","first-page":"3038","DOI":"10.1016\/j.bbamcr.2014.09.015","article-title":"Decline in cellular clearance systems induces inflammasome signaling in human ARPE-19 cells","volume":"1843","author":"Piippo","year":"2014","journal-title":"Biochim Biophys Acta"},{"key":"2022022809442494800_sct312794-bib-0049","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1038\/nature10744","article-title":"Galectin 8 targets damaged vesicles for autophagy to defend cells against bacterial invasion","volume":"482","author":"Thurston","year":"2012","journal-title":"Nature"},{"issue":"1","key":"2022022809442494800_sct312794-bib-0050","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.molcel.2018.03.009","article-title":"Galectins control mTOR in response to endomembrane damage","volume":"70","author":"Jia","year":"2018","journal-title":"Mol Cell"},{"key":"2022022809442494800_sct312794-bib-0051","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1111\/j.1365-2133.2000.03725.x","article-title":"Heterozygous HPS1 mutations in a case of Hermansky-Pudlak syndrome with giant melanosomes","volume":"143","author":"Horikawa","year":"2000","journal-title":"Br J Dermatol"},{"key":"2022022809442494800_sct312794-bib-0052","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/ncomms3111","article-title":"Spatiotemporally controlled induction of autophagy-mediated lysosome turnover","volume":"4","author":"Hung","year":"2013","journal-title":"Nat Commun"},{"key":"2022022809442494800_sct312794-bib-0053","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1091\/mbc.e14-05-1028","article-title":"Cholesterol-mediated activation of acid sphingomyelinase disrupts autophagy in the retinal pigment epithelium","volume":"26","author":"Toops","year":"2015","journal-title":"Mol Biol Cell"},{"key":"2022022809442494800_sct312794-bib-0054","doi-asserted-by":"crossref","first-page":"9014","DOI":"10.1073\/pnas.1805039115","article-title":"Aberrant early endosome biogenesis mediates complement activation in the retinal pigment epithelium in models of macular degeneration","volume":"115","author":"Kaur","year":"2018","journal-title":"Proc Natl Acad Sci USA"},{"key":"2022022809442494800_sct312794-bib-0055","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-018-28143-0","article-title":"C3a triggers formation of sub-retinal pigment epithelium deposits via the ubiquitin proteasome pathway","volume":"8","author":"Fernandez-Godino","year":"2018","journal-title":"Sci Rep"},{"key":"2022022809442494800_sct312794-bib-0056","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1016\/j.ajpath.2013.04.008","article-title":"Complement component C3 plays a critical role in protecting the aging retina in a murine model of age-related macular degeneration","volume":"183","author":"Hoh Kam","year":"2013","journal-title":"Am J Pathol"},{"key":"2022022809442494800_sct312794-bib-0057","doi-asserted-by":"crossref","first-page":"3436","DOI":"10.1167\/iovs.10-6002","article-title":"Expression of complement component 3 (C3) from an adenovirus leads to pathology in the murine retina","volume":"52","author":"Cashman","year":"2011","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"2022022809442494800_sct312794-bib-0058","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.3389\/fimmu.2019.01007","article-title":"The challenges and promise of complement therapeutics for ocular diseases","volume":"10","author":"Park","year":"2019","journal-title":"Front Immunol"},{"key":"2022022809442494800_sct312794-bib-0059","doi-asserted-by":"crossref","first-page":"2413","DOI":"10.2147\/DDDT.S206355","article-title":"Complement system and age-related macular degeneration: drugs and challenges","volume":"13","author":"Wu","year":"2019","journal-title":"Drug des Devel Ther"},{"key":"2022022809442494800_sct312794-bib-0060","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1007\/978-1-4419-5635-4_9","article-title":"Peptide inhibitor of complement C3 activation, on cynomolgus monkey with early-onset macular degeneration","volume":"703","author":"Chi","year":"2010","journal-title":"Adv Exp Med Biol"},{"key":"2022022809442494800_sct312794-bib-0061","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1038\/s41573-019-0031-6","article-title":"Clinical promise of next-generation complement therapeutics","volume":"18","author":"Mastellos","year":"2019","journal-title":"Nat Rev Drug Discov"},{"key":"2022022809442494800_sct312794-bib-0062","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1111\/j.1365-2818.1993.tb03313.x","article-title":"Measurement of co-localization of objects in dual-colour confocal images","volume":"169","author":"Manders","year":"1993","journal-title":"J Microsc"}],"container-title":["Stem Cells Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/sctm.20-0211","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/sctm.20-0211","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/stcltm\/article-pdf\/9\/12\/1585\/42628635\/stcltm_9_12_1585.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/stcltm\/article-pdf\/9\/12\/1585\/42628635\/stcltm_9_12_1585.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,28]],"date-time":"2022-02-28T10:03:12Z","timestamp":1646042592000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/stcltm\/article\/9\/12\/1585\/6407010"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,20]]},"references-count":62,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2020,8,20]]},"published-print":{"date-parts":[[2020,12,1]]}},"URL":"https:\/\/doi.org\/10.1002\/sctm.20-0211","relation":{},"ISSN":["2157-6564","2157-6580"],"issn-type":[{"value":"2157-6564","type":"print"},{"value":"2157-6580","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,12,1]]},"published":{"date-parts":[[2020,8,20]]},"assertion":[{"value":"2020-05-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-07-12","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-08-20","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}