{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T02:21:14Z","timestamp":1789179674756,"version":"build-2803163510"},"reference-count":172,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2022,10,31]],"date-time":"2022-10-31T00:00:00Z","timestamp":1667174400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Age-related macular degeneration (AMD) is a complex and multifactorial disease, resulting from the interaction of environmental and genetic factors. The continuous discovery of associations between genetic polymorphisms and AMD gives reason for the pivotal role attributed to the genetic component to its development. In that light, genetic tests and polygenic scores have been created to predict the risk of development and response to therapy. Still, none of them have yet been validated. Furthermore, there is no evidence from a clinical trial that the determination of the individual genetic structure can improve treatment outcomes. In this comprehensive review, we summarize the polymorphisms of the main pathogenetic ways involved in AMD development to identify which of them constitutes a potential therapeutic target. As complement overactivation plays a major role, the modulation of targeted complement proteins seems to be a promising therapeutic approach. Herein, we summarize the complement-modulating molecules now undergoing clinical trials, enlightening those in an advanced phase of trial. Gene therapy is a potential innovative one-time treatment, and its relevance is quickly evolving in the field of retinal diseases. We describe the state of the art of gene therapies now undergoing clinical trials both in the field of complement-suppressors and that of anti-VEGF.<\/jats:p>","DOI":"10.3390\/ijms232113280","type":"journal-article","created":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T06:01:28Z","timestamp":1667282488000},"page":"13280","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Genetic Aspects of Age-Related Macular Degeneration and Their Therapeutic Potential"],"prefix":"10.3390","volume":"23","author":[{"given":"Elisa","family":"Stradiotto","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20072 Milan, Italy"},{"name":"Department of Ophthalmology, Eye Unit Humanitas Gavazzeni-Castelli, Via Mazzini 11, 24128 Bergamo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Allegrini","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Eye Unit Humanitas Gavazzeni-Castelli, Via Mazzini 11, 24128 Bergamo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3374-8539","authenticated-orcid":false,"given":"Giovanni","family":"Fossati","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20072 Milan, Italy"},{"name":"Department of Ophthalmology, Eye Unit Humanitas Gavazzeni-Castelli, Via Mazzini 11, 24128 Bergamo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8472-7984","authenticated-orcid":false,"given":"Raffaele","family":"Raimondi","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20072 Milan, Italy"},{"name":"Department of Ophthalmology, Eye Unit Humanitas Gavazzeni-Castelli, Via Mazzini 11, 24128 Bergamo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tania","family":"Sorrentino","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20072 Milan, Italy"},{"name":"Department of Ophthalmology, Eye Unit Humanitas Gavazzeni-Castelli, Via Mazzini 11, 24128 Bergamo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4984-5496","authenticated-orcid":false,"given":"Domenico","family":"Tripepi","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20072 Milan, Italy"},{"name":"Department of Ophthalmology, Eye Unit Humanitas Gavazzeni-Castelli, Via Mazzini 11, 24128 Bergamo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8734-0186","authenticated-orcid":false,"given":"Gianmaria","family":"Barone","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20072 Milan, Italy"},{"name":"Department of Ophthalmology, Eye Unit Humanitas Gavazzeni-Castelli, Via Mazzini 11, 24128 Bergamo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8110-0027","authenticated-orcid":false,"given":"Antonio","family":"Inforzato","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20072 Milan, Italy"},{"name":"IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano-Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario R.","family":"Romano","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20072 Milan, Italy"},{"name":"Department of Ophthalmology, Eye Unit Humanitas Gavazzeni-Castelli, Via Mazzini 11, 24128 Bergamo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,31]]},"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. 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