{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T06:12:19Z","timestamp":1778825539747,"version":"3.51.4"},"reference-count":69,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T00:00:00Z","timestamp":1778803200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>Retinal degenerative diseases are among the leading causes of irreversible vision loss worldwide and arise primarily from progressive dysfunction and death of photoreceptors and retinal pigment epithelial (RPE) cells. Because the mammalian retina lacks an intrinsic capacity for regeneration, current treatments remain limited and largely palliative. Recent advances in stem cell technologies and gene-based therapies, however, have opened new avenues for retinal repair and functional restoration. Among monogenic retinal disorders, BEST1-associated retinopathies provide a particularly informative paradigm for linking molecular mechanisms to emerging regenerative strategies.The human BEST1 encodes bestrophin-1 (BEST1), a calcium-activated chloride channel predominantly expressed in the RPE, where it plays essential roles in ionic homeostasis, transepithelial transport, and regulation of the visual cycle. Pathogenic variants in BEST1 give rise to a spectrum of inherited retinal diseases, including Best vitelliform macular dystrophy, autosomal recessive bestrophinopathy, and adult-onset vitelliform dystrophy. Mechanistic studies of BEST1 mutations have revealed diverse functional consequences, ranging from loss-of-function to gain-of-function effects, highlighting the importance of precise molecular diagnosis for therapeutic intervention.Here, we synthesize recent progress in stem cell\u2013derived RPE models and gene correction strategies, using BEST1-associated retinopathies as a conceptual framework. We discuss how human induced pluripotent stem cell\u2013derived RPE systems enable disease modeling and functional analysis of pathogenic variants, and how gene replacement and genome editing approaches are tailored to distinct mutation classes. Finally, we explore how integration of stem cell and gene therapy strategies may advance retinal regeneration and outline future directions for personalized and mechanism-based treatments of retinal degenerative diseases.<\/jats:p>","DOI":"10.3389\/fcell.2026.1832772","type":"journal-article","created":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T05:42:48Z","timestamp":1778823768000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["From BEST1 mutations to retinal regeneration: integrating stem cell\u2013derived RPE models and gene correction strategies"],"prefix":"10.3389","volume":"14","author":[{"given":"Yan","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Columbia University","place":["New York, NY, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sihua","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Columbia University","place":["New York, NY, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Columbia University","place":["New York, NY, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tingting","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Columbia University","place":["New York, NY, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"287","DOI":"10.4103\/sjopt.sjopt_175_23","article-title":"Gene therapy in bestrophinopathies: insights from preclinical studies in preparation for clinical trials","volume":"37","author":"Amato","year":"2023","journal-title":"Saudi J. 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