{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T18:09:14Z","timestamp":1779127754186,"version":"3.51.4"},"reference-count":52,"publisher":"American Society for Clinical Investigation","issue":"12","license":[{"start":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T00:00:00Z","timestamp":1750809600000},"content-version":"vor","delay-in-days":50,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Guangdong Provincial Key Area R&D Program","award":["2023B1111050004"],"award-info":[{"award-number":["2023B1111050004"]}]},{"name":"Guangzhou Science and Technology Plan Project","award":["2024B01J1121,2025A03J3988"],"award-info":[{"award-number":["2024B01J1121,2025A03J3988"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82101329,82271095"],"award-info":[{"award-number":["82101329,82271095"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100012166","name":"National Key R&D Program of China","doi-asserted-by":"crossref","award":["2018YFA0108300"],"award-info":[{"award-number":["2018YFA0108300"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01EY035897,R01EY035549"],"award-info":[{"award-number":["R01EY035897,R01EY035549"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,6,23]]},"abstract":"<jats:p>\n                    Inherited retinal degenerations (IRDs) are important causes of progressive, irreversible blindness. Hereditary macular diseases, in particular, are significant in their effect on the specialized, central cone photoreceptor\u2013rich macula responsible for high resolution vision. Autosomal dominant Best vitelliform macular dystrophy (BVMD), caused by variants in the\n                    <jats:italic>BEST1<\/jats:italic>\n                    gene, is one of the most common inherited macular dystrophies. Gene therapies have emerged as promising treatments for IRDs, but a lack of suitable animal models has hindered progress both in treatments and in understanding the mechanisms underlying macular diseases. Here, we report a\n                    <jats:italic>Macaca fascicularis<\/jats:italic>\n                    carrying a heterozygous potential pathogenic\n                    <jats:italic>BEST1p.Q327E<\/jats:italic>\n                    variant that disrupts the BEST1 ion channel by destabilizing the A195 helix, mirroring the structural perturbations seen in certain human pathological mutants. Longitudinal imaging over 2 years revealed progressive macular changes, including subfoveal cleft enlargement, lipid-rich deposit accumulation, retinal pigment epithelium (RPE) disruption, and central-to-peripheral photoreceptor degeneration, recapitulating early human BVMD pathology. Histopathology demonstrated diminished BEST1 expression, attenuation of the RPE-photoreceptor interface, and 2 distinct types of lipid deposits, including heretofore unappreciated cone mitochondrial-enriched lesions, highlighting selective cone mitochondria vulnerability. This is, to our knowledge, the first nonhuman primate model of inherited macular dystrophy, and it links\n                    <jats:italic>BEST1<\/jats:italic>\n                    mutations, mitochondrial dysfunction, and progressive macular degeneration, offering new insights into BVMD pathophysiology and highlighting its utility for studying disease progression and potential therapeutic interventions.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.190807","type":"journal-article","created":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T12:00:17Z","timestamp":1746532817000},"source":"Crossref","is-referenced-by-count":4,"title":["A spontaneous nonhuman primate model of inherited retinal degeneration"],"prefix":"10.1172","volume":"10","author":[{"given":"Wei","family":"Yi","sequence":"first","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingming","family":"Xu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Xue","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China."},{"name":"Department of Ophthalmology, Affiliated Hospital of Nantong University, Nantong, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingxue","family":"Cao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China."},{"name":"Department of Ophthalmology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ziqi","family":"Yang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9321-9348","authenticated-orcid":true,"given":"Lingli","family":"Zhou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China."},{"name":"Department of Ophthalmology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Zhou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Le","family":"Shi","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China."},{"name":"Department of Ophthalmology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaomei","family":"Mai","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3040-4279","authenticated-orcid":true,"given":"Zehui","family":"Sun","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenjie","family":"Qing","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuying","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aolun","family":"Qing","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaiwen","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lechun","family":"Ou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shoudeng","family":"Chen","sequence":"additional","affiliation":[{"name":"Central Laboratory, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elia J.","family":"Duh","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xialin","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"232","published-online":{"date-parts":[[2025,5,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2024.101306"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)31868-8"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/7.9.1517"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2017.01.006"},{"key":"B5","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1007\/978-3-319-95046-4_29","article-title":"Best vitelliform macular dystrophy","volume":"1085","author":"Tsang","year":"2018","journal-title":"Adv Exp Med Biol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2009.04.002"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/S0161-6420(81)34965-3"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-010-0821-5"},{"issue":"13","key":"B9","first-page":"2672","article-title":"BESTROPHIN1 mutations cause defective chloride conductance in patient stem cell-derived RPE","volume":"25","author":"Moshfegh","year":"2016","journal-title":"Hum Mol Genet"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.15-18168"},{"key":"B11","first-page":"347","article-title":"Bestrophin-1 influences transepithelial electrical properties and Ca2+ signaling in human retinal pigment epithelium","volume":"21","author":"Marmorstein","year":"2015","journal-title":"Mol Vis"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2017.01.005"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1167\/tvst.10.6.7"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3390\/genes13020344"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1172\/JCI123980"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.64.11.23"},{"issue":"9","key":"B17","first-page":"485","article-title":"Inherited macular dystrophies and differential diagnostics","volume":"48","author":"Liutkevi\u010dien\u0117","year":"2012","journal-title":"Medicina (Kaunas)"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24119722"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-49922-6"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-31437-7"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2021.10466"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2014.02.006"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3109\/13816810.2015.1020558"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.123.11.1588"},{"key":"B25","first-page":"575","article-title":"Multimodal analysis of the progression of Best vitelliform macular dystrophy","volume":"20","author":"Querques","year":"2014","journal-title":"Mol Vis"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajo.2019.08.011"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2016.11.022"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajo.2008.05.029"},{"key":"B29","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/B978-0-444-64032-1.00033-3","article-title":"The electrooculogram","volume":"160","author":"Creel","year":"2019","journal-title":"Handb Clin Neurol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2014.02.023"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddp583"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.63.4.1"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1007\/s004410000225"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.06-0868"},{"key":"B35","article-title":"The cell biology of the retinal pigment epithelium","author":"Lakkaraju","journal-title":"Prog Retin Eye Res"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23073661"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.10-6707"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.29914"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.1982.01030040093017"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.1988.01060140421045"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1097\/00006982-200412000-00014"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2004.10.041"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.62.6.22"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2001776117"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abn2070"},{"key":"B46","first-page":"60","article-title":"Three-dimensional analysis of mouse rod and cone mitochondrial cristae architecture: bioenergetic and functional implications","volume":"9","author":"Perkins","year":"2003","journal-title":"Mol Vis"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1007\/s00417-022-05684-9"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.112115"},{"issue":"4","key":"B49","first-page":"214","article-title":"Application of the genome editing tool CRISPR\/Cas9 in non-human primates","volume":"37","author":"Luo","year":"2016","journal-title":"Dongwuxue Yanjiu"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1016\/j.scib.2020.09.008"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2024.101244"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1007\/s10633-022-09872-0"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/190807\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T17:36:16Z","timestamp":1779125776000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/190807"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,6]]},"references-count":52,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,5,6]]},"published-print":{"date-parts":[[2025,6,23]]}},"alternative-id":["10.1172\/jci.insight.190807"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.190807","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,6]]},"article-number":"e190807"}}