{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T07:10:40Z","timestamp":1791443440835,"version":"4.3.3"},"reference-count":88,"publisher":"American Society for Clinical Investigation","issue":"8","license":[{"start":{"date-parts":[[2025,4,22]],"date-time":"2025-04-22T00:00:00Z","timestamp":1745280000000},"content-version":"vor","delay-in-days":49,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key Research and Development Program of China","award":["2021YFC2700902"],"award-info":[{"award-number":["2021YFC2700902"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["31970557"],"award-info":[{"award-number":["31970557"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,4,22]]},"abstract":"<jats:p>\n                    Leber hereditary optic neuropathy (LHON) is a paradigm for mitochondrial retinopathy due to mitochondrial DNA (mtDNA) mutations. However, the mechanism underlying retinal cell\u2013specific effects of LHON-linked mtDNA mutations remains poorly understood, and there has been no effective treatment or cure for this disorder. Using a mouse model bearing an LHON-linked ND6\n                    <jats:sup>P25L<\/jats:sup>\n                    mutation, we demonstrated that the mutation caused retinal cell\u2013specific deficiencies, especially in retinal ganglion cells (RGCs), rods, and M\u00fcller cells. Single-cell RNA sequencing revealed cell-specific dysregulation of oxidative phosphorylation and visual signaling pathways in the mutant retina. Strikingly, ND6 mutation\u2013induced dysfunctions caused abnormal vitamin A (VA) metabolism essential for visual function. VA supplementation remarkably alleviated retinal deficiencies, including reduced fundus lesion and retinal thickness and increased numbers of RGCs, photoreceptors, and M\u00fcller cell neurites. The restoration of visual functions with VA treatment were further evidenced by correcting dysregulations of phototransduction cascade and neurotransmitter transmission and restoring electrophysiological properties. Interestingly, VA supplementation markedly rescued the abnormal mitochondrial morphologies and functions in the mutant retina. These findings provide insight into retina-specific pathophysiology of mitochondrial retinopathy arising from VA deficiency and mitochondrial dysfunction induced by mtDNA mutation and a step toward therapeutic intervention for LHON and other mitochondrial retinopathies.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.188962","type":"journal-article","created":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T12:00:47Z","timestamp":1741089647000},"source":"Crossref","is-referenced-by-count":6,"title":["Vitamin A treatment restores vision failures arising from Leber\u2019s hereditary optic neuropathy\u2013linked mtDNA mutation"],"prefix":"10.1172","volume":"10","author":[{"given":"Cheng","family":"Ai","sequence":"first","affiliation":[{"name":"Center for Mitochondrial Biomedicine and Department of Ophthalmology, the Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, China."},{"name":"Institute of Genetics, Zhejiang University, Hangzhou, China."},{"name":"Center for Genetic Medicine, Zhejiang University International School and Institute of Medicine, Yiwu, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-7582-6368","authenticated-orcid":true,"given":"Huiying","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Genetics, Zhejiang University, Hangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyan","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Genetics, Zhejiang University, Hangzhou, China."},{"name":"Zhejiang Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases, Women\u2019s Hospital, Zhejiang University School of Medicine, Hangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3924-7006","authenticated-orcid":true,"given":"Yanchun","family":"Ji","sequence":"additional","affiliation":[{"name":"Institute of Genetics, Zhejiang University, Hangzhou, China."},{"name":"Division of Medical Genetics and Genomics, The Children\u2019s Hospital, Zhejiang University School of Medicine and National Clinical Research Center for Child Health, Hangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas C.","family":"Wallace","sequence":"additional","affiliation":[{"name":"Center for Mitochondrial and Epigenomic Medicine, Children\u2019s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1483-1836","authenticated-orcid":true,"given":"Junbin","family":"Qian","sequence":"additional","affiliation":[{"name":"Institute of Genetics, Zhejiang University, Hangzhou, China."},{"name":"Zhejiang Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases, Women\u2019s Hospital, Zhejiang University School of Medicine, Hangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yimin","family":"Zhu","sequence":"additional","affiliation":[{"name":"Zhejiang Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases, Women\u2019s Hospital, Zhejiang University School of Medicine, Hangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5067-6736","authenticated-orcid":true,"given":"Min-Xin","family":"Guan","sequence":"additional","affiliation":[{"name":"Center for Mitochondrial Biomedicine and Department of Ophthalmology, the Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, China."},{"name":"Institute of Genetics, Zhejiang University, Hangzhou, China."},{"name":"Center for Genetic Medicine, Zhejiang University International School and Institute of Medicine, Yiwu, China."},{"name":"Zhejiang Provincial Key Laboratory of Genetic and Developmental Disorders, Zhejiang University, Hangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2025,3,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.10.002"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2014.06.003"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2020.01.005"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.02.051"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2024.101264"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23010210"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2019.10.008"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1126\/science.aal5060"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/S1350-9462(02)00012-5"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbabio.2009.02.024"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1007\/164_2017_2"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1007\/s11940-010-0100-y"},{"issue":"5","key":"B13","first-page":"295","article-title":"Clinical spectrum of Leber\u2019s hereditary optic neuropathy","volume":"4","author":"Kerrison","year":"1997","journal-title":"Clin Neurosci"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajo.2005.03.017"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1126\/science.3201231"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.14-16158"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1002\/humu.1380060405"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1080\/02713689808951221"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awm114"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110119200"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddv498"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddn303"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA120.014603"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.62.9.38"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1172\/JCI134965"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.111124"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1217113109"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23031014"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.3390\/nu8110746"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1021\/cr400107q"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8227(01)00331-X"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1096\/fj.08-112375"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M053652"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1001\/jamaophthalmol.2018.0590"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21041380"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2019.04.010"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2018100811"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4463"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.54279"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/s0092-8674(00)80439-0"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1038\/nn1155"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1038\/nature23283"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0425-3"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abq1533"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-023-02907-z"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.genet.39.110304.095751"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.05.045"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1007\/s00232-012-9463-1"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1126\/science.1136244"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2021.101013"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2022.101111"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.17.7854"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)00011-8"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1038\/303169a0"},{"key":"B55"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-024-01839-8"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddac109"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2008.02.004"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.182209"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddv045"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2020.165743"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2017.07.025"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.2147\/EB.S9078"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1139\/y92-257"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1186\/s12929-023-00951-1"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2015.05.039"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2018.08.002"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-022-03605-2"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1126\/science.2218545"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddu258"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0503460102"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1093\/pnasnexus\/pgad167"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.3390\/antiox11061142"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(22)00174-0"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1097\/ICU.0000000000000891"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.3390\/cells10051202"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2021.101101"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.121.000806"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.11-8476"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.119.258517"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.12-9662"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1126\/science.1147786"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(81)90300-7"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac698"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA117.000317"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddac032"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2024.114153"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.10-6138"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/188962\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T20:04:13Z","timestamp":1779134653000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/188962"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,4]]},"references-count":88,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,3,4]]},"published-print":{"date-parts":[[2025,4,22]]}},"alternative-id":["10.1172\/jci.insight.188962"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.188962","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,4]]},"article-number":"e188962"}}