{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T12:58:12Z","timestamp":1769605092489,"version":"3.49.0"},"reference-count":73,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T00:00:00Z","timestamp":1676332800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001602","name":"Science Foundation Ireland","doi-asserted-by":"publisher","award":["16\/IA\/4452"],"award-info":[{"award-number":["16\/IA\/4452"]}],"id":[{"id":"10.13039\/501100001602","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001602","name":"Science Foundation Ireland","doi-asserted-by":"publisher","award":["EI CF-2019-1106-Y"],"award-info":[{"award-number":["EI CF-2019-1106-Y"]}],"id":[{"id":"10.13039\/501100001602","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001602","name":"Science Foundation Ireland","doi-asserted-by":"publisher","award":["HRAPOR-2015-1140"],"award-info":[{"award-number":["HRAPOR-2015-1140"]}],"id":[{"id":"10.13039\/501100001602","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001602","name":"Science Foundation Ireland","doi-asserted-by":"publisher","award":["StarT 813490"],"award-info":[{"award-number":["StarT 813490"]}],"id":[{"id":"10.13039\/501100001602","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001602","name":"Science Foundation Ireland","doi-asserted-by":"publisher","award":["MRCG-2016-14"],"award-info":[{"award-number":["MRCG-2016-14"]}],"id":[{"id":"10.13039\/501100001602","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001588","name":"Enterprise Ireland","doi-asserted-by":"publisher","award":["16\/IA\/4452"],"award-info":[{"award-number":["16\/IA\/4452"]}],"id":[{"id":"10.13039\/501100001588","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001588","name":"Enterprise Ireland","doi-asserted-by":"publisher","award":["EI CF-2019-1106-Y"],"award-info":[{"award-number":["EI CF-2019-1106-Y"]}],"id":[{"id":"10.13039\/501100001588","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001588","name":"Enterprise Ireland","doi-asserted-by":"publisher","award":["HRAPOR-2015-1140"],"award-info":[{"award-number":["HRAPOR-2015-1140"]}],"id":[{"id":"10.13039\/501100001588","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001588","name":"Enterprise Ireland","doi-asserted-by":"publisher","award":["StarT 813490"],"award-info":[{"award-number":["StarT 813490"]}],"id":[{"id":"10.13039\/501100001588","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001588","name":"Enterprise Ireland","doi-asserted-by":"publisher","award":["MRCG-2016-14"],"award-info":[{"award-number":["MRCG-2016-14"]}],"id":[{"id":"10.13039\/501100001588","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Health Research Board Ireland","award":["16\/IA\/4452"],"award-info":[{"award-number":["16\/IA\/4452"]}]},{"name":"Health Research Board Ireland","award":["EI CF-2019-1106-Y"],"award-info":[{"award-number":["EI CF-2019-1106-Y"]}]},{"name":"Health Research Board Ireland","award":["HRAPOR-2015-1140"],"award-info":[{"award-number":["HRAPOR-2015-1140"]}]},{"name":"Health Research Board Ireland","award":["StarT 813490"],"award-info":[{"award-number":["StarT 813490"]}]},{"name":"Health Research Board Ireland","award":["MRCG-2016-14"],"award-info":[{"award-number":["MRCG-2016-14"]}]},{"name":"EU Marie Curie Innovative Training Network","award":["16\/IA\/4452"],"award-info":[{"award-number":["16\/IA\/4452"]}]},{"name":"EU Marie Curie Innovative Training Network","award":["EI CF-2019-1106-Y"],"award-info":[{"award-number":["EI CF-2019-1106-Y"]}]},{"name":"EU Marie Curie Innovative Training Network","award":["HRAPOR-2015-1140"],"award-info":[{"award-number":["HRAPOR-2015-1140"]}]},{"name":"EU Marie Curie Innovative Training Network","award":["StarT 813490"],"award-info":[{"award-number":["StarT 813490"]}]},{"name":"EU Marie Curie Innovative Training Network","award":["MRCG-2016-14"],"award-info":[{"award-number":["MRCG-2016-14"]}]},{"name":"Fighting Blindness Ireland\u2014Health Research Charities Ireland","award":["16\/IA\/4452"],"award-info":[{"award-number":["16\/IA\/4452"]}]},{"name":"Fighting Blindness Ireland\u2014Health Research Charities Ireland","award":["EI CF-2019-1106-Y"],"award-info":[{"award-number":["EI CF-2019-1106-Y"]}]},{"name":"Fighting Blindness Ireland\u2014Health Research Charities Ireland","award":["HRAPOR-2015-1140"],"award-info":[{"award-number":["HRAPOR-2015-1140"]}]},{"name":"Fighting Blindness Ireland\u2014Health Research Charities Ireland","award":["StarT 813490"],"award-info":[{"award-number":["StarT 813490"]}]},{"name":"Fighting Blindness Ireland\u2014Health Research Charities Ireland","award":["MRCG-2016-14"],"award-info":[{"award-number":["MRCG-2016-14"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Age-related macular degeneration (AMD) is the most common cause of blindness in the aged population. However, to date there is no effective treatment for the dry form of the disease, representing 85\u201390% of cases. AMD is an immensely complex disease which affects, amongst others, both retinal pigment epithelium (RPE) and photoreceptor cells and leads to the progressive loss of central vision. Mitochondrial dysfunction in both RPE and photoreceptor cells is emerging as a key player in the disease. There are indications that during disease progression, the RPE is first impaired and RPE dysfunction in turn leads to subsequent photoreceptor cell degeneration; however, the exact sequence of events has not as yet been fully determined. We recently showed that AAV delivery of an optimised NADH-ubiquinone oxidoreductase (NDI1) gene, a nuclear-encoded complex 1 equivalent from S. cerevisiae, expressed from a general promoter, provided robust benefit in a variety of murine and cellular models of dry AMD; this was the first study employing a gene therapy to directly boost mitochondrial function, providing functional benefit in vivo. However, use of a restricted RPE-specific promoter to drive expression of the gene therapy enables exploration of the optimal target retinal cell type for dry AMD therapies. Furthermore, such restricted transgene expression could reduce potential off-target effects, possibly improving the safety profile of the therapy. Therefore, in the current study, we interrogate whether expression of the gene therapy from the RPE-specific promoter, Vitelliform macular dystrophy 2 (VMD2), might be sufficient to rescue dry AMD models.<\/jats:p>","DOI":"10.3390\/ijms24043847","type":"journal-article","created":{"date-parts":[[2023,2,15]],"date-time":"2023-02-15T03:09:21Z","timestamp":1676430561000},"page":"3847","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["RPE-Directed Gene Therapy Improves Mitochondrial Function in Murine Dry AMD Models"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7470-0702","authenticated-orcid":false,"given":"Sophia","family":"Millington-Ward","sequence":"first","affiliation":[{"name":"The School of Genetics and Microbiology, Smurfit Institute of Genetics, Trinity College Dublin, D02 VF25 Dublin, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1684-1598","authenticated-orcid":false,"given":"Naomi","family":"Chadderton","sequence":"additional","affiliation":[{"name":"The School of Genetics and Microbiology, Smurfit Institute of Genetics, Trinity College Dublin, D02 VF25 Dublin, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3395-1211","authenticated-orcid":false,"given":"Laura K.","family":"Finnegan","sequence":"additional","affiliation":[{"name":"The School of Genetics and Microbiology, Smurfit Institute of Genetics, Trinity College Dublin, D02 VF25 Dublin, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iris J. M.","family":"Post","sequence":"additional","affiliation":[{"name":"The School of Genetics and Microbiology, Smurfit Institute of Genetics, Trinity College Dublin, D02 VF25 Dublin, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew","family":"Carrigan","sequence":"additional","affiliation":[{"name":"The School of Genetics and Microbiology, Smurfit Institute of Genetics, Trinity College Dublin, D02 VF25 Dublin, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachel","family":"Nixon","sequence":"additional","affiliation":[{"name":"The School of Genetics and Microbiology, Smurfit Institute of Genetics, Trinity College Dublin, D02 VF25 Dublin, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marian M.","family":"Humphries","sequence":"additional","affiliation":[{"name":"The School of Genetics and Microbiology, Smurfit Institute of Genetics, Trinity College Dublin, D02 VF25 Dublin, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pete","family":"Humphries","sequence":"additional","affiliation":[{"name":"The School of Genetics and Microbiology, Smurfit Institute of Genetics, Trinity College Dublin, D02 VF25 Dublin, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul F.","family":"Kenna","sequence":"additional","affiliation":[{"name":"The School of Genetics and Microbiology, Smurfit Institute of Genetics, Trinity College Dublin, D02 VF25 Dublin, Ireland"},{"name":"The Research Foundation, Royal Victoria Eye and Ear Hospital, D02 XK51 Dublin, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arpad","family":"Palfi","sequence":"additional","affiliation":[{"name":"The School of Genetics and Microbiology, Smurfit Institute of Genetics, Trinity College Dublin, D02 VF25 Dublin, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G. Jane","family":"Farrar","sequence":"additional","affiliation":[{"name":"The School of Genetics and Microbiology, Smurfit Institute of Genetics, Trinity College Dublin, D02 VF25 Dublin, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1080\/07853890600946724","article-title":"Age-related macular degeneration--emerging pathogenetic and therapeutic concepts","volume":"38","author":"Gehrs","year":"2006","journal-title":"Ann. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1001\/archopht.123.3.321","article-title":"The US twin study of age-related macular degeneration: Relative roles of genetic and environmental influences","volume":"123","author":"Seddon","year":"2005","journal-title":"Arch. Ophthalmol."},{"key":"ref_3","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_4","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1159\/000455074","article-title":"The Journey of \u201cGeographic Atrophy\u201d through Past, Present, and Future","volume":"237","year":"2017","journal-title":"Ophthalmologica"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1016\/j.ajhg.2021.05.015","article-title":"Beyond factor H: The impact of genetic-risk variants for age-related macular degeneration on circulating factor-H-like 1 and factor-H-related protein concentrations","volume":"108","author":"Cipriani","year":"2021","journal-title":"Am. J. Hum. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1765","DOI":"10.1007\/s00018-016-2147-8","article-title":"Inflammation and its role in age-related macular degeneration","volume":"73","author":"Kauppinen","year":"2016","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"AMD Gene Consortium (2013). Seven new loci associated with age-related macular degeneration. Nat. Genet., 45, 433\u2013439.","DOI":"10.1038\/ng.2578"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e14319","DOI":"10.7554\/eLife.14319","article-title":"Hypoxia-induced metabolic stress in retinal pigment epithelial cells is sufficient to induce photoreceptor degeneration","volume":"5","author":"Kurihara","year":"2016","journal-title":"Elife"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1016\/j.neurobiolaging.2005.05.012","article-title":"Mitochondrial alterations of retinal pigment epithelium in age-related macular degeneration","volume":"27","author":"Feher","year":"2006","journal-title":"Neurobiol. Aging"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"100858","DOI":"10.1016\/j.preteyeres.2020.100858","article-title":"Mechanisms of mitochondrial dysfunction and their impact on age-related macular degeneration","volume":"79","author":"Kaarniranta","year":"2020","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e2537","DOI":"10.1038\/cddis.2016.453","article-title":"Dysfunctional autophagy in RPE, a contributing factor in age-related macular degeneration","volume":"8","author":"Golestaneh","year":"2017","journal-title":"Cell Death Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.redox.2017.05.015","article-title":"Altered bioenergetics and enhanced resistance to oxidative stress in human retinal pigment epithelial cells from donors with age-related macular degeneration","volume":"13","author":"Ferrington","year":"2017","journal-title":"Redox Biol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Viiri, J., Amadio, M., Marchesi, N., Hyttinen, J.M., Kivinen, N., Sironen, R., Rilla, K., Akhtar, S., Provenzani, A., and D\u2019Agostino, V.G. (2013). Autophagy activation clears ELAVL1\/HuR-mediated accumulation of SQSTM1\/p62 during proteasomal inhibition in human retinal pigment epithelial cells. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0069563"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2848","DOI":"10.1167\/iovs.07-1352","article-title":"Mitochondrial proteomics of the retinal pigment epithelium at progressive stages of age-related macular degeneration","volume":"49","author":"Nordgaard","year":"2008","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1007\/s00417-018-3984-y","article-title":"Tear film proteome in age-related macular degeneration","volume":"256","author":"Winiarczyk","year":"2018","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"15440","DOI":"10.1038\/s41598-019-51777-7","article-title":"Proteome and Secretome Dynamics of Human Retinal Pigment Epithelium in Response to Reactive Oxygen Species","volume":"9","author":"Meyer","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1016\/j.redox.2014.04.006","article-title":"Oxygen delivery, consumption, and conversion to reactive oxygen species in experimental models of diabetic retinopathy","volume":"2","author":"Eshaq","year":"2014","journal-title":"Redox Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3793","DOI":"10.1038\/s41598-019-40507-8","article-title":"Phagosomal and mitochondrial alterations in RPE may contribute to KCNJ13 retinopathy","volume":"7","author":"Toms","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1016\/j.bbalip.2016.07.013","article-title":"Lipids, oxidized lipids, oxidation-specific epitopes, and Age-related Macular Degeneration","volume":"1862","author":"Handa","year":"2017","journal-title":"Biochim. Biophys. Acta Mol. Cell Biol. Lipids"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"101781","DOI":"10.1016\/j.redox.2020.101781","article-title":"Complement activation, lipid metabolism, and mitochondrial injury: Converging pathways in age-related macular degeneration","volume":"37","author":"Tan","year":"2020","journal-title":"Redox Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.preteyeres.2017.03.002","article-title":"The impact of oxidative stress and inflammation on RPE degeneration in non-neovascular AMD","volume":"60","author":"Datta","year":"2017","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Keeling, E., Lotery, A.J., Tumbarello, D.A., and Ratnayaka, J.A. (2018). Impaired Cargo Clearance in the Retinal Pigment Epithelium (RPE) Underlies Irreversible Blinding Diseases. Cells, 7.","DOI":"10.20944\/preprints201801.0269.v1"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Blasiak, J., Pawlowska, E., Szczepanska, J., and Kaarniranta, K. (2019). Interplay between Autophagy and the Ubiquitin-Proteasome System and Its Role in the Pathogenesis of Age-Related Macular Degeneration. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20010210"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.molmed.2019.10.008","article-title":"Mitochondrial Defects Drive Degenerative Retinal Diseases","volume":"26","author":"Ferrington","year":"2020","journal-title":"Trends Mol. Med."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Kim, J., Lee, Y.J., and Won, J.Y. (2021). Molecular Mechanisms of Retinal Pigment Epithelium Dysfunction in Age-Related Macular Degeneration. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222212298"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"101201","DOI":"10.1016\/j.redox.2019.101201","article-title":"Mitochondrial oxidative stress in the retinal pigment epithelium (RPE) led to metabolic dysfunction in both the RPE and retinal photoreceptors","volume":"24","author":"Brown","year":"2019","journal-title":"Redox Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"AMD41","DOI":"10.1167\/iovs.18-24289","article-title":"Perspective on AMD Pathobiology: A Bioenergetic Crisis in the RPE","volume":"59","author":"Fisher","year":"2018","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"7304","DOI":"10.1523\/JNEUROSCI.0190-15.2015","article-title":"Investigating mitochondria as a target for treating age-related macular degeneration","volume":"35","author":"Terluk","year":"2015","journal-title":"J. Neurosci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"7901270","DOI":"10.1155\/2020\/7901270","article-title":"Central Role of Oxidative Stress in Age-Related Macular Degeneration: Evidence from a Review of the Molecular Mechanisms and Animal Models","volume":"2020","author":"Abokyi","year":"2020","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1038\/ng912","article-title":"Uncontrolled C3 activation causes membranoproliferative glomerulonephritis in mice deficient in complement factor H","volume":"31","author":"Pickering","year":"2002","journal-title":"Nat. Genet."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"16651","DOI":"10.1073\/pnas.0705079104","article-title":"Complement factor H deficiency in aged mice causes retinal abnormalities and visual dysfunction","volume":"104","author":"Coffey","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_32","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_33","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_34","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_35","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_36","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":"Lenassi","year":"2013","journal-title":"Am. J. Pathol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e3040","DOI":"10.1073\/pnas.1424391112","article-title":"Regulation of age-related macular degeneration-like pathology by complement factor H","volume":"112","author":"Toomey","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e952","DOI":"10.1002\/ctm2.952","article-title":"AAV-mediated gene therapy improving mitochondrial function provides benefit in age-related macular degeneration models","volume":"12","author":"Chadderton","year":"2022","journal-title":"Clin. Transl. Med."},{"key":"ref_39","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_40","doi-asserted-by":"crossref","first-page":"4487","DOI":"10.1007\/s00018-021-03796-9","article-title":"The complement system in age-related macular degeneration","volume":"78","author":"Armento","year":"2021","journal-title":"Cell Mol. Life Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1136\/bjo.25.2.62","article-title":"The nature of experimental degeneration of the retina","volume":"25","author":"Sorsby","year":"1941","journal-title":"Br. J. Ophthalmol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"101681","DOI":"10.1016\/j.redox.2020.101681","article-title":"The retinal pigment epithelium in Sorsby Fundus Dystrophy shows increased sensitivity to oxidative stress-induced degeneration","volume":"37","author":"Wolk","year":"2020","journal-title":"Redox Biol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Enzbrenner, A., Zulliger, R., Biber, J., Pousa, A.M.Q., Sch\u00e4fer, N., Stucki, C., Giroud, N., Berrera, M., Kortvely, E., and Schmucki, R. (2021). Sodium Iodate-Induced Degeneration Results in Local Complement Changes and Inflammatory Processes in Murine Retina. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22179218"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1859","DOI":"10.1016\/S0042-6989(97)00015-1","article-title":"Functional recovery of retina after sodium iodate injection in mice","volume":"37","author":"Mizota","year":"1997","journal-title":"Vision Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2209","DOI":"10.1016\/j.celrep.2020.01.064","article-title":"Toll-like Receptor 2 Facilitates Oxidative Damage-Induced Retinal Degeneration","volume":"30","author":"Mulfaul","year":"2020","journal-title":"Cell Rep."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1016\/j.brainres.2016.04.021","article-title":"Endoplasmic reticulum stress in human photoreceptor diseases","volume":"1648","author":"Chan","year":"2016","journal-title":"Brain Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1038\/s41419-018-0331-5","article-title":"Light action spectrum on oxidative stress and mitochondrial damage in A2E-loaded retinal pigment epithelium cells","volume":"9","author":"Marie","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.exer.2016.01.018","article-title":"Increased retinal mtDNA damage in the CFH variant associated with age-related macular degeneration","volume":"145","author":"Ferrington","year":"2016","journal-title":"Exp. Eye Res."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Fisher, C.R., Ebeling, M.C., Geng, Z., Kapphahn, R.J., Roehrich, H., Montezuma, S.R., Dutton, J.R., and Ferrington, D.A. (2022). Human iPSC- and Primary-Retinal Pigment Epithelial Cells for Modeling Age-Related Macular Degeneration. Antioxidants, 11.","DOI":"10.3390\/antiox11040605"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"115168","DOI":"10.1016\/j.bcp.2022.115168","article-title":"Treatment and prevention of pathological mitochondrial dysfunction in retinal degeneration and in photoreceptor injury","volume":"203","author":"Moos","year":"2022","journal-title":"Biochem. Pharmacol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1038\/nature19095","article-title":"Structure of mammalian respiratory complex I","volume":"536","author":"Zhu","year":"2016","journal-title":"Nature"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"926627","DOI":"10.3389\/fragi.2022.926627","article-title":"Role of Mitochondria in Retinal Pigment Epithelial Aging and Degeneration","volume":"3","author":"Tong","year":"2022","journal-title":"Front. Aging"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"19064","DOI":"10.1074\/jbc.M309881200","article-title":"Analysis of the VMD2 promoter and implication of E-box binding factors in its regulation","volume":"279","author":"Esumi","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_54","first-page":"1047","article-title":"Superoxide production by porcine retinal pigment epithelium in vitro","volume":"30","author":"Dorey","year":"1989","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"7154","DOI":"10.1073\/pnas.130110497","article-title":"Biosynthesis of a major lipofuscin fluorophore in mice and humans with ABCR-mediated retinal and macular degeneration","volume":"97","author":"Mata","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"4164","DOI":"10.1073\/pnas.0407698102","article-title":"Lipofuscin accumulation, abnormal electrophysiology, and photoreceptor degeneration in mutant ELOVL4 transgenic mice: A model for macular degeneration","volume":"102","author":"Karan","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1016\/j.celrep.2019.12.082","article-title":"Integration of eQTL and a Single-Cell Atlas in the Human Eye Identifies Causal Genes for Age-Related Macular Degeneration","volume":"30","author":"Orozco","year":"2020","journal-title":"Cell Rep."},{"key":"ref_58","first-page":"2815","article-title":"Retinal pigment epithelial cell distribution in central retina of rhesus monkeys","volume":"43","author":"Snodderly","year":"2002","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.preteyeres.2005.11.002","article-title":"Visual function and dysfunction in early and late age-related maculopathy","volume":"25","author":"Hogg","year":"2006","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1001\/archophthalmol.2008.622","article-title":"Cone degeneration in aging and age-related macular degeneration","volume":"127","author":"Shelley","year":"2009","journal-title":"Arch. Ophthalmol."},{"key":"ref_61","first-page":"2015","article-title":"Spare the rods, save the cones in aging and age-related maculopathy","volume":"41","author":"Curcio","year":"2000","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1097\/IAE.0b013e318265801d","article-title":"Investigation of oral fenretinide for treatment of geographic atrophy in age-related macular degeneration","volume":"33","author":"Mata","year":"2013","journal-title":"Retina"},{"key":"ref_63","first-page":"184","article-title":"Amyloid-beta is found in drusen from some age-related macular degeneration retinas, but not in drusen from normal retinas","volume":"9","author":"Dentchev","year":"2003","journal-title":"Mol. Vis."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Hoh Kam, J., Lenassi, E., and Jeffery, G. (2010). Viewing ageing eyes: Diverse sites of amyloid Beta accumulation in the ageing mouse retina and the up-regulation of macrophages. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0013127"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"E279","DOI":"10.1073\/pnas.1100901108","article-title":"Anti-amyloid therapy protects against retinal pigmented epithelium damage and vision loss in a model of age-related macular degeneration","volume":"108","author":"Ding","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.1002\/sctm.20-0211","article-title":"Complement modulation reverses pathology in Y402H-retinal pigment epithelium cell model of age-related macular degeneration by restoring lysosomal function","volume":"9","author":"Cerniauskas","year":"2020","journal-title":"Stem Cells Transl. Med."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1038\/s41434-021-00239-9","article-title":"Functional expression of complement factor I following AAV-mediated gene delivery in the retina of mice and human cells","volume":"28","author":"Dreismann","year":"2021","journal-title":"Gene Ther."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"E11120","DOI":"10.1073\/pnas.1802519115","article-title":"Expression of ABCA4 in the retinal pigment epithelium and its implications for Stargardt macular degeneration","volume":"115","author":"Lenis","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/j.omtm.2022.03.016","article-title":"AAV-PHP.eB transduces both the inner and outer retina with high efficacy in mice","volume":"25","author":"Palfi","year":"2022","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Arnault, E., Barrau, C., Nanteau, C., Gondouin, P., Bigot, K., Vi\u00e9not, F., Gutman, E., Fontaine, V., Villette, T., and Cohen-Tannoudji, D. (2013). Phototoxic action spectrum on a retinal pigment epithelium model of age-related macular degeneration exposed to sunlight normalized conditions. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0071398"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1089\/hum.2009.119","article-title":"Adeno-associated virus-mediated rhodopsin replacement provides therapeutic benefit in mice with a targeted disruption of the rhodopsin gene","volume":"21","author":"Palfi","year":"2010","journal-title":"Hum. Gene Ther."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.stemcr.2020.05.007","article-title":"Modeling and Rescue of RP2 Retinitis Pigmentosa Using iPSC-Derived Retinal Organoids","volume":"15","author":"Lane","year":"2020","journal-title":"Stem Cell Rep."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1038\/ejhg.2012.112","article-title":"Intravitreal delivery of AAV-NDI1 provides functional benefit in a murine model of Leber hereditary optic neuropathy","volume":"21","author":"Chadderton","year":"2013","journal-title":"Eur. J. Hum. Genet"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/4\/3847\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:35:31Z","timestamp":1760121331000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/4\/3847"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,14]]},"references-count":73,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["ijms24043847"],"URL":"https:\/\/doi.org\/10.3390\/ijms24043847","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,14]]}}}