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Degeneration\/dysregulation of the retinal pigment epithelium (RPE), a supportive monolayer of cells underlying the photoreceptors, is commonly seen in patients with AMD. While treatment exists for the neovascular\/wet form of AMD, there is currently no cure for the non\u2010exudative\/dry form of AMD, making it imperative to understand the pathogenesis of this disease. Although our understanding of the aetiology of AMD has increased over the years, the underlying disease mechanism has not yet been identified, mainly due to the multifactorial nature of this disease. Herein, we review some of the commonly proposed degeneration pathways of RPE cells and their role in the pathogenesis of AMD; including activation of the complement cascade, oxidative stress\u2010induced cell death mechanisms, dysfunctional mitochondria and the role of crystallins in AMD disease progression.<\/jats:p>","DOI":"10.1111\/ceo.13834","type":"journal-article","created":{"date-parts":[[2020,7,25]],"date-time":"2020-07-25T01:14:23Z","timestamp":1595639663000},"page":"1043-1056","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":190,"title":["Retinal pigment epithelium and age\u2010related macular degeneration: A review of major disease mechanisms"],"prefix":"10.1111","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3379-9360","authenticated-orcid":false,"given":"Shreya","family":"Somasundaran","sequence":"first","affiliation":[{"name":"Centre for Ophthalmology and Visual Science\/Lions Eye Institute University of Western Australia  Nedlands Western Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2140-6478","authenticated-orcid":false,"given":"Ian J.","family":"Constable","sequence":"additional","affiliation":[{"name":"Centre for Ophthalmology and Visual Science\/Lions Eye Institute University of Western Australia  Nedlands Western Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3685-6516","authenticated-orcid":false,"given":"Carla B.","family":"Mellough","sequence":"additional","affiliation":[{"name":"Centre for Ophthalmology and Visual Science\/Lions Eye Institute University of Western Australia  Nedlands Western Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3909-5778","authenticated-orcid":false,"given":"Livia S.","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Centre for Ophthalmology and Visual Science\/Lions Eye Institute University of Western Australia  Nedlands Western Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,8,17]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1080\/07853890600946724"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1710430114"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.61.1.1"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4835(88)90025-5"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/bjo.2005.086579"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2013.07.003"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00021.2004"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2020.101004"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.eye.6700460"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/IAE.0000000000001392"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1159\/000455074"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.16-20781"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2017.08.038"},{"key":"e_1_2_10_15_1","unstructured":"HagemanGS GehrsK JohnsonLV AndersonD. 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