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Though these pigmentary changes are hallmarks of disease progression, it is unknown if their presence is protective or detrimental.<\/jats:p>\n                  <jats:p>\n                    Here, we first evaluated the impact of pigment plaques on vascular changes and disease progression in MacTel. In a retrospective, longitudinal study, we analyzed multimodal retinal images of patients with MacTel and showed that pigment plaques were associated with decreased vascular leakage and stabilized neovascular growth. We then modeled the underlying pathomechanisms of pigment plaque formation in aberrant neovascular growth using the very-low-density lipoprotein receptor mutant (\n                    <jats:italic>Vldlr<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ) mouse. Our data indicated that during RPE-proliferation, migration and accumulation along neovessels RPE-cells underwent epithelial-mesenchymal transition (EMT). Pharmacologic inhibition of EMT in\n                    <jats:italic>Vldlr<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice decreased pigment coverage, and exacerbated neovascular growth and vascular leakage.\n                  <\/jats:p>\n                  <jats:p>Our findings indicate that the proliferation, migration and perivascular accumulation of RPE-cells stabilize vascular proliferation and exudation, thereby exerting a protective effect on the diseased retina. We conclude that interfering with this \u201cnatural repair mechanism\u201d may have detrimental effects on the course of the disease and should thus be avoided.<\/jats:p>","DOI":"10.1007\/s10456-024-09954-4","type":"journal-article","created":{"date-parts":[[2024,11,27]],"date-time":"2024-11-27T07:09:58Z","timestamp":1732691398000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Retinal pigment epithelial cells reduce vascular leak and proliferation in retinal neovessels"],"prefix":"10.1007","volume":"28","author":[{"given":"Simone","family":"Tzaridis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edith","family":"Aguilar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael I.","family":"Dorrell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Friedlander","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin T.","family":"Eade","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,11,27]]},"reference":[{"key":"9954_CR1","doi-asserted-by":"publisher","first-page":"100969","DOI":"10.1016\/j.preteyeres.2021.100969","volume":"85","author":"SM George","year":"2021","unstructured":"George SM, Lu F, Rao M, Leach LL, Gross JM (2021) The retinal pigment epithelium: development, injury responses, and regenerative potential in mammalian and non-mammalian systems. 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Arch Ophthalmol 125(6):795\u2013803. https:\/\/doi.org\/10.1001\/archopht.125.6.795","journal-title":"Arch Ophthalmol"}],"container-title":["Angiogenesis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10456-024-09954-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10456-024-09954-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10456-024-09954-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T10:06:13Z","timestamp":1739354773000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10456-024-09954-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,27]]},"references-count":44,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,2]]}},"alternative-id":["9954"],"URL":"https:\/\/doi.org\/10.1007\/s10456-024-09954-4","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2024.07.15.24306102","asserted-by":"object"},{"id-type":"doi","id":"10.21203\/rs.3.rs-4960014\/v1","asserted-by":"object"}]},"ISSN":["0969-6970","1573-7209"],"issn-type":[{"value":"0969-6970","type":"print"},{"value":"1573-7209","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,27]]},"assertion":[{"value":"22 August 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 October 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 November 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The studies were approved by the local ethics committees at each participating study site (Comit\u00e9 consultatif de protection des personnes dans la recherche biom\u00e9dicale (CCPPRB); Human Research Ethics Committee (HREC); London City Road & Hampstead Research Ethics Committee; Sterling Institutional Review Board; Ethik-Kommission der \u00c4rztekammer Westfalen-Lippe und der Medizinischen Fakult\u00e4t der WWU M\u00fcnster; The State of Israel Ministry of Health; The Chaim Sheba Medical Center; Ethik-Kommission - Medizinische Fakult\u00e4t Bonn; University of Pennsylvania Institutional Review Board; Kantonale Ethikkommission Bern (KEK); University of Miami Human Subject Research Office), and were in adherence with the Declaration of Helsinki. All participants provided informed consent prior to participation. All animal experimental procedures were approved by The Scripps Research Institute Animal Care and Use Committee. Experiments were performed in accordance with the NIH Guide for the Care and Use of Laboratory Animals (National Academies Press, 2011).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"1"}}