{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T10:17:47Z","timestamp":1791454667789,"version":"4.3.3"},"reference-count":106,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T00:00:00Z","timestamp":1755216000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82201212"],"award-info":[{"award-number":["82201212"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2023NSFSC1670"],"award-info":[{"award-number":["2023NSFSC1670"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Natural Science Foundation of Sichuan Province","award":["82201212"],"award-info":[{"award-number":["82201212"]}]},{"name":"Natural Science Foundation of Sichuan Province","award":["2023NSFSC1670"],"award-info":[{"award-number":["2023NSFSC1670"]}]},{"name":"Claffy Foundation Bright Idea Grant","award":["82201212"],"award-info":[{"award-number":["82201212"]}]},{"name":"Claffy Foundation Bright Idea Grant","award":["2023NSFSC1670"],"award-info":[{"award-number":["2023NSFSC1670"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Replacement of the retinal pigment epithelium (RPE) is emerging as a promising approach to treat degenerative retinal diseases, including age-related macular degeneration and Stargardt disease, in which RPE function cannot otherwise be restored. Despite the limitations of existing treatments, advances in cell sourcing and surgical methods have enabled initial human trials of RPE transplantation, with early results indicating potential efficacy. This review comprehensively examines the evolution of RPE transplantation in recent decades, highlighting the advantages and limitations of different cell sources and delivery methods. Current clinical trial data are analyzed with a particular focus on immune rejection risks, surgical complications, and long-term safety. Despite encouraging safety profiles, achieving consistent and sustained visual improvement remains a challenge, as vision outcomes might be influenced by factors such as disease stage at intervention, transplantation site, number of cells transplanted, and duration of follow-up. Key challenges, such as cell or graft survival and integration with the host retina, are discussed in depth, as overcoming these obstacles is essential for achieving stable and effective RPE replacement. Future research directions, including innovations in biomaterials, molecular modification strategies, and personalized approaches, hold promise for enhancing the efficacy and durability of RPE transplantation for retinal disease.<\/jats:p>","DOI":"10.3390\/biom15081167","type":"journal-article","created":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T08:39:07Z","timestamp":1755247147000},"page":"1167","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Retinal Pigment Epithelium Transplantation in Retinal Disease: Clinical Trial Development, Challenges, and Future Directions"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0865-0441","authenticated-orcid":false,"given":"Qin","family":"Chen","sequence":"first","affiliation":[{"name":"The Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Zhang","sequence":"additional","affiliation":[{"name":"Save Sight Institute, University of Sydney, Sydney, NSW 2015, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi","family":"Chen","sequence":"additional","affiliation":[{"name":"Intelligent Polymer Research Institute, University of Wollongong, Wollongong, NSW 2522, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingwen","family":"Zeng","sequence":"additional","affiliation":[{"name":"Save Sight Institute, University of Sydney, Sydney, NSW 2015, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4594-5423","authenticated-orcid":false,"given":"Aine","family":"O\u2019Connor","sequence":"additional","affiliation":[{"name":"New South Wales Tissue Bank, Sydney Eye Hospital, New South Wales Organ and Tissue Donation Service, Sydney, NSW 2000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meidong","family":"Zhu","sequence":"additional","affiliation":[{"name":"Save Sight Institute, University of Sydney, Sydney, NSW 2015, Australia"},{"name":"New South Wales Tissue Bank, Sydney Eye Hospital, New South Wales Organ and Tissue Donation Service, Sydney, NSW 2000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8580-0274","authenticated-orcid":false,"given":"Mark C.","family":"Gillies","sequence":"additional","affiliation":[{"name":"Save Sight Institute, University of Sydney, Sydney, NSW 2015, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Lu","sequence":"additional","affiliation":[{"name":"The Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0776-1630","authenticated-orcid":false,"given":"Ling","family":"Zhu","sequence":"additional","affiliation":[{"name":"Save Sight Institute, University of Sydney, Sydney, NSW 2015, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"100846","DOI":"10.1016\/j.preteyeres.2020.100846","article-title":"The Cell Biology of the Retinal Pigment Epithelium","volume":"78","author":"Lakkaraju","year":"2020","journal-title":"Prog. 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