{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T03:16:57Z","timestamp":1792811817494,"version":"4.5.0"},"reference-count":40,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T00:00:00Z","timestamp":1763942400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"crossref","award":["RS-2025-02217948"],"award-info":[{"award-number":["RS-2025-02217948"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"crossref","award":["RS-2024-00452984"],"award-info":[{"award-number":["RS-2024-00452984"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Soonchunhyang University Research fund","id":[{"id":"https:\/\/ror.org\/03qjsrb10","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>To address the shortcomings of existing anti-VEGF monotherapy in neovascular age-related macular degeneration (nAMD), we investigated the therapeutic capabilities of exosomes obtained from human induced pluripotent stem cell (hiPSC)-derived retinal organoids in a mouse model of laser-induced choroidal neovascularization (CNV). To evaluate Retinal Organoid-derived exosome (RO-Exo) distribution after intravitreal (IVT) injection, calcein-labeled RO-Exo was observed using confocal microscopy. CNV was induced in C57BL\/6 J mice by laser photocoagulation. RO-Exo was isolated from retinal organoids (differentiation days 55\u201365) and injected 5 days post-laser. Therapeutic efficacy was evaluated on day 12. Vascular leakage and CNV size were assessed by angiography and CD31 immunostaining. We also examined HIF-1\u03b1\/VEGF-A expression (Western blotting), Retinal Pigment Epithelium (RPE) integrity markers (immunofluorescence staining for \u03b1-SMA, fibronectin, and ZO-1), and the activation of the Mitogen-Activated Protein Kinase (MAPK) pathway (phospho-ERK, -p38, -JNK) in CNV lesions. After IVT injection, RO-Exo migrated to the RPE layer, showing high retinotropic distribution. In the CNV model, RO-Exo significantly reduced vascular leakage and CNV size, with greater suppression of HIF-1\u03b1 and VEGFA expression than aflibercept, the standard-of-care anti-VEGF drug. CD31-positive vasculature was decreased, accompanied by downregulation of fibronectin (a fibrotic marker) and restoration of RPE hexagonality and integrity. Furthermore, RO-Exo inhibited the activation of ERK, P38, and JNK in CNV lesions. Our study results demonstrate that RO-Exo exhibits multi-target therapeutic effects\u2014including anti-angiogenic, anti-fibrotic, and neuroprotective actions\u2014offering a promising alternative to conventional anti-VEGF therapy for nAMD.<\/jats:p>","DOI":"10.3390\/ijms262311327","type":"journal-article","created":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T09:02:07Z","timestamp":1763974927000},"page":"11327","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Retinal Organoid-Derived Exosomes Reduce CNV Lesion and Restore RPE Integrity in Mouse Laser-Induced Choroidal Neovascularization (CNV) Model"],"prefix":"10.3390","volume":"26","author":[{"given":"Jin Young","family":"Yang","sequence":"first","affiliation":[{"name":"Laboratory for Translational Research on Retinal and Macular Degeneration, Soonchunhyang University Bucheon Hospital, Bucheon 14584, Republic of Korea"},{"name":"Department of Ophthalmology, Soonchunhyang University Bucheon Hospital, Bucheon 14584, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeji","family":"Kim","sequence":"additional","affiliation":[{"name":"Laboratory for Translational Research on Retinal and Macular Degeneration, Soonchunhyang University Bucheon Hospital, Bucheon 14584, Republic of Korea"},{"name":"Department of Interdisciplinary Program in Biomedical Science, Soonchunhyang Graduate School, Soonchunhyang University Bucheon Hospital, Bucheon 14584, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumin","family":"An","sequence":"additional","affiliation":[{"name":"Laboratory for Translational Research on Retinal and Macular Degeneration, Soonchunhyang University Bucheon Hospital, Bucheon 14584, Republic of Korea"},{"name":"Department of Interdisciplinary Program in Biomedical Science, Soonchunhyang Graduate School, Soonchunhyang University Bucheon Hospital, Bucheon 14584, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung Woo","family":"Han","sequence":"additional","affiliation":[{"name":"Laboratory for Translational Research on Retinal and Macular Degeneration, Soonchunhyang University Bucheon Hospital, Bucheon 14584, Republic of Korea"},{"name":"Department of Ophthalmology, Soonchunhyang University Bucheon Hospital, Bucheon 14584, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun-Sub","family":"Choi","sequence":"additional","affiliation":[{"name":"Laboratory for Translational Research on Retinal and Macular Degeneration, Soonchunhyang University Bucheon Hospital, Bucheon 14584, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9689-4384","authenticated-orcid":false,"given":"Tae Kwann","family":"Park","sequence":"additional","affiliation":[{"name":"Laboratory for Translational Research on Retinal and Macular Degeneration, Soonchunhyang University Bucheon Hospital, Bucheon 14584, Republic of Korea"},{"name":"Department of Ophthalmology, Soonchunhyang University Bucheon Hospital, Bucheon 14584, Republic of Korea"},{"name":"Department of Interdisciplinary Program in Biomedical Science, Soonchunhyang Graduate School, Soonchunhyang University Bucheon Hospital, Bucheon 14584, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e106","DOI":"10.1016\/S2214-109X(13)70145-1","article-title":"Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: A systematic review and meta-analysis","volume":"2","author":"Wong","year":"2020","journal-title":"Lancet Glob. 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