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Current treatments relying on intravitreal (IVT) administration of anti-angiogenic agents are costly and of moderate effectiveness. Metformin, the common anti-diabetic drug, has been associated with decreased odds of developing AMD. Studies have shown that metformin can mitigate cellular aging, neoangiogenesis, and inflammation across multiple diseases. This preclinical study assessed metformin\u2019s impact on vessel growth using choroidal explants before exploring IVT metformin\u2019s effects on laser-induced CNV and light-induced retinal degeneration in C57BL\/6J and BALB\/cJ mice, respectively. Metformin reduced new vessel growth in choroidal explants in a dose-dependent relationship. Following laser induction, IVT metformin suppressed CNV and decreased peripheral infiltration of IBA1+ macrophages\/microglia. Furthermore, IVT metformin protected against retinal thinning in response to light-induced degeneration. IVT metformin downregulated genes in the choroid and retinal pigment epithelium which are associated with angiogenesis and inflammation, two key processes that drive nAMD progression. These findings underscore metformin\u2019s capacity as an anti-angiogenic and neuroprotective agent, demonstrating this drug\u2019s potential as an accessible option to help manage nAMD.<\/jats:p>","DOI":"10.3390\/ijms252111357","type":"journal-article","created":{"date-parts":[[2024,10,22]],"date-time":"2024-10-22T07:53:43Z","timestamp":1729583623000},"page":"11357","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Intravitreal Metformin Protects Against Choroidal Neovascularization and Light-Induced Retinal Degeneration"],"prefix":"10.3390","volume":"25","author":[{"given":"Jason F.","family":"Xiao","sequence":"first","affiliation":[{"name":"Department of Ophthalmology and Visual Science, University of Chicago, Chicago, IL 60637, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Science, University of Chicago, Chicago, IL 60637, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4417-622X","authenticated-orcid":false,"given":"Amir","family":"Mani","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Science, University of Chicago, Chicago, IL 60637, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugo","family":"Barba","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Science, University of Chicago, Chicago, IL 60637, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7190-7852","authenticated-orcid":false,"given":"Aniruddhsingh","family":"Solanki","sequence":"additional","affiliation":[{"name":"Animal Resources Center, University of Chicago, Chicago, IL 60637, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Droho","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0884-1336","authenticated-orcid":false,"given":"Jeremy A.","family":"Lavine","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitra","family":"Skondra","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Science, University of Chicago, Chicago, IL 60637, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,22]]},"reference":[{"key":"ref_1","unstructured":"GBD 2019 Blindness and Vision Impairment Collaborators, and Vision Loss Expert Group of the Global Burden of Disease Study (2021). 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