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Although vascular endothelial growth factor (VEGF) inhibition effectively suppresses vascular leakage and neovascularization, some patients still develop fibrosis and experience irreversible vision loss. Recent studies have identified multiple interconnected signaling pathways that contribute to fibrotic progression, highlighting the potential need for combination or multitargeted therapeutic strategies. This review summarizes the cellular origins of myofibroblasts, the molecular mechanisms underlying fibrosis, and recent advances in antifibrotic therapies. We particularly highlight the angio-fibrotic switch, mesenchymal transition, cellular stress responses, extracellular matrix remodeling, mechanotransduction, and emerging therapeutic approaches for ocular fibrosis. Relevant preclinical and clinical studies were identified through searches of PubMed and clinical trial registries.<\/jats:p>","DOI":"10.3390\/cells15191772","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T12:09:25Z","timestamp":1790683765000},"page":"1772","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Fibrotic Remodeling in Retinal Vascular Diseases: Cellular Origins, Molecular Mechanisms, and Therapeutic Perspectives"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-7356-6836","authenticated-orcid":false,"given":"Jia Yu","family":"Ning","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Regenerative Medicine, University of Illinois College of Medicine, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Regenerative Medicine, University of Illinois College of Medicine, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miyuki Ishida","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Regenerative Medicine, University of Illinois College of Medicine, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4075-9866","authenticated-orcid":false,"given":"Kaori H.","family":"Yamada","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Regenerative Medicine, University of Illinois College of Medicine, Chicago, IL 60612, USA"},{"name":"Department of Ophthalmology and Visual Sciences, University of Illinois College of Medicine, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"The Lancet Diabetes Endocrinology (2020). 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