{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T22:02:56Z","timestamp":1791928976337,"version":"4.3.4"},"reference-count":40,"publisher":"Association for Research in Vision and Ophthalmology (ARVO)","issue":"5","license":[{"start":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:00:00Z","timestamp":1779926400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Invest. Ophthalmol. Vis. Sci."],"published-print":{"date-parts":[[2026,5,28]]},"DOI":"10.1167\/iovs.67.5.71","type":"journal-article","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T13:30:48Z","timestamp":1779975048000},"page":"71","source":"Crossref","is-referenced-by-count":0,"title":["Oxidative Stress\u2013Induced Age-Related Bullous Keratopathy in Corneal Endothelial Cells With Lipid Droplets and Vacuoles"],"prefix":"10.1167","volume":"67","author":[{"given":"Hiromi","family":"Onouchi","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Tokai University School of Medicine, Kanagawa, Japan"},{"name":"Department of Ophthalmology, International University Health and Welfare, Atami Hospital, Shizuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Yamasaki","sequence":"additional","affiliation":[{"name":"Department of Molecular Life Science, Tokai University School of Medicine, Kanagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rikuto","family":"Toda","sequence":"additional","affiliation":[{"name":"Department of Molecular Life Science, Tokai University School of Medicine, Kanagawa, Japan"},{"name":"Course of Life Science and Technology, Graduate School of Science and Technology, Tokai University, Kanagawa, Japan"},{"name":"Course of Longevity and Resilience, Department of Molecular Life Science, Tokai University School of Medicine, Kanagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiyasu","family":"Taniguchi","sequence":"additional","affiliation":[{"name":"Department of Molecular Life Science, Tokai University School of Medicine, Kanagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Tokai University School of Medicine, Kanagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuyuki","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Tokai University School of Medicine, Kanagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoaki","family":"Ishii","sequence":"additional","affiliation":[{"name":"Office of Professor Emeritus, Kanagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takamasa","family":"Ishii","sequence":"additional","affiliation":[{"name":"Department of Molecular Life Science, Tokai University School of Medicine, Kanagawa, Japan"},{"name":"Course of Longevity and Resilience, Department of Molecular Life Science, Tokai University School of Medicine, Kanagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"27","reference":[{"issue":"6809","key":"bib1","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1038\/35041687","article-title":"Oxidants, oxidative stress and the biology of ageing","volume":"408","author":"Finkel","year":"2000","journal-title":"Nature"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.freeradbiomed.2014.01.004","article-title":"Oxidative stress induces mitochondrial dysfunction and a protective unfolded protein response in RPE cells","volume":"69","author":"Cano","year":"2014","journal-title":"Free Radic Biol Med"},{"issue":"6694","key":"bib3","doi-asserted-by":"publisher","first-page":"694","DOI":"10.1038\/29331","article-title":"A mutation in succinate dehydrogenase cytochrome b causes oxidative stress and ageing in nematodes","volume":"394","author":"Ishii","year":"1998","journal-title":"Nature"},{"issue":"3","key":"bib4","doi-asserted-by":"publisher","first-page":"552","DOI":"10.3390\/cells11030552","article-title":"Oxidative stress in human pathology and aging: molecular mechanisms and perspectives","volume":"11","author":"Hajam","year":"2022","journal-title":"Cells"},{"issue":"10","key":"bib5","doi-asserted-by":"publisher","first-page":"2499","DOI":"10.1007\/s00204-023-03562-9","article-title":"Reactive oxygen species, toxicity, oxidative stress, and antioxidants: chronic diseases and aging","volume":"97","author":"Jomova","year":"2023","journal-title":"Arch Toxicol"},{"issue":"1","key":"bib6","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1111\/acel.12523","article-title":"Endogenous reactive oxygen species cause astrocyte defects and neuronal dysfunctions in the hippocampus: a new model for aging brain","volume":"16","author":"Ishii","year":"2017","journal-title":"Aging Cell"},{"issue":"3","key":"bib7","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1161\/CIRCRESAHA.114.300559","article-title":"Cardiac mitochondria and reactive oxygen species generation","volume":"114","author":"Chen","year":"2014","journal-title":"Circ Res"},{"issue":"2","key":"bib8","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1159\/000335675","article-title":"Mitochondria and oxidative stress in the cardiorenal metabolic syndrome","volume":"2","author":"Aroor","year":"2012","journal-title":"Cardiorenal Med"},{"issue":"1","key":"bib9","doi-asserted-by":"publisher","first-page":"454","DOI":"10.1007\/s11033-024-09425-5","article-title":"The role of oxidative stress in the pathogenesis of ocular diseases: an overview","volume":"51","author":"Zhang","year":"2024","journal-title":"Mol Biol Rep"},{"issue":"3","key":"bib10","first-page":"837","article-title":"The role of oxidative stress in the aging eye","volume":"13","author":"Goodman","year":"2023","journal-title":"Life (Basel)"},{"key":"bib11","doi-asserted-by":"publisher","first-page":"101201","DOI":"10.1016\/j.redox.2019.101201","article-title":"Mitochondrial oxidative stress in the retinal pigment epithelium (RPE) led to metabolic dysfunction in both the RPE and retinal photoreceptors","volume":"24","author":"Brown","year":"2019","journal-title":"Redox Biol"},{"key":"bib12","doi-asserted-by":"publisher","first-page":"591530","DOI":"10.1155\/2015\/591530","article-title":"Oxidative stress to the cornea, changes in corneal optical properties, and advances in treatment of corneal oxidative injuries","volume":"2015","author":"Cejka","year":"2015","journal-title":"Oxid Med Cell Longev"},{"issue":"4","key":"bib13","doi-asserted-by":"publisher","first-page":"e412","DOI":"10.1111\/aos.13526","article-title":"Dry eye disease and oxidative stress","volume":"96","author":"Seen","year":"2018","journal-title":"Acta Ophthalmol"},{"issue":"14","key":"bib14","doi-asserted-by":"publisher","first-page":"DES163","DOI":"10.1167\/iovs.17-23402","article-title":"Potential role of oxidative stress in ocular surface inflammation and dry eye disease","volume":"59","author":"Dogru","year":"2018","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"10","key":"bib15","doi-asserted-by":"publisher","first-page":"e45805","DOI":"10.1371\/journal.pone.0045805","article-title":"Oxidative stress induced inflammation initiates functional decline of tear production","volume":"7","author":"Uchino","year":"2012","journal-title":"PLoS One"},{"key":"bib16","first-page":"443","article-title":"Investigation of oxidative stress in pterygium tissue","volume":"17","author":"Balci","year":"2011","journal-title":"Mol Vis"},{"issue":"6","key":"bib17","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1097\/ICL.0000000000000620","article-title":"Oxidative stress and genotoxicity in pterygium: a systemic investigation","volume":"45","author":"Kilic-Toprak","year":"2019","journal-title":"Eye Contact Lens"},{"key":"bib18","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.preteyeres.2015.07.002","article-title":"Progress in corneal wound healing","volume":"49","author":"Ljubimov","year":"2015","journal-title":"Prog Retin Eye Res"},{"key":"bib19","doi-asserted-by":"publisher","first-page":"108495","DOI":"10.1016\/j.exer.2021.108495","article-title":"Diseases of the corneal endothelium","volume":"205","author":"Jeang","year":"2021","journal-title":"Exp Eye Res"},{"issue":"9","key":"bib20","doi-asserted-by":"publisher","first-page":"5780","DOI":"10.1167\/iovs.12-9573","article-title":"Mitochondrial superoxide anion overproduction in Tet-mev-1 transgenic mice accelerates age-dependent corneal cell dysfunctions","volume":"53","author":"Onouchi","year":"2012","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"1","key":"bib21","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1016\/j.mito.2010.09.006","article-title":"Mitochondrial reactive oxygen species generation by the SDHC V69E mutation causes low birth weight and neonatal growth retardation","volume":"11","author":"Ishii","year":"2011","journal-title":"Mitochondrion"},{"issue":"4","key":"bib22","doi-asserted-by":"publisher","first-page":"668","DOI":"10.3390\/cells12040668","article-title":"Autophagosome biogenesis","volume":"12","author":"Zhen","year":"2023","journal-title":"Cells"},{"issue":"6","key":"bib23","doi-asserted-by":"publisher","first-page":"912","DOI":"10.3390\/biom13060912","article-title":"The Janus-faced role of lipid droplets in aging: insights from the cellular perspective","volume":"13","author":"Bresgen","year":"2023","journal-title":"Biomolecules"},{"key":"bib24","doi-asserted-by":"publisher","first-page":"101635","DOI":"10.1016\/j.redox.2020.101635","article-title":"Exercise and dietary intervention ameliorate high-fat diet-induced NAFLD and liver aging by inducing lipophagy","volume":"36","author":"Gao","year":"2020","journal-title":"Redox Biol"},{"issue":"11","key":"bib25","doi-asserted-by":"publisher","first-page":"1031","DOI":"10.1038\/s41419-021-04326-y","article-title":"Lipophagy deficiency exacerbates ectopic lipid accumulation and tubular cells injury in diabetic nephropathy","volume":"12","author":"Han","year":"2021","journal-title":"Cell Death Dis"},{"issue":"12","key":"bib26","doi-asserted-by":"publisher","first-page":"1067","DOI":"10.1016\/j.tins.2023.09.006","article-title":"Lysosomes in retinal health and disease","volume":"46","author":"Boya","year":"2023","journal-title":"Trends Neurosci"},{"issue":"3","key":"bib27","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1055\/s-0039-1685524","article-title":"Lipid droplet formation and lipophagy in fatty liver disease","volume":"39","author":"Schulze","year":"2019","journal-title":"Semin Liver Dis"},{"issue":"18","key":"bib28","doi-asserted-by":"publisher","first-page":"2999","DOI":"10.1007\/s00018-012-0962-0","article-title":"Mitochondrial dysfunction and oxidative stress activate inflammasomes: Impact on the aging process and age-related diseases","volume":"69","author":"Salminen","year":"2012","journal-title":"Cell Mol Life Sci"},{"issue":"7182","key":"bib29","doi-asserted-by":"publisher","first-page":"1069","DOI":"10.1038\/nature06639","article-title":"Autophagy fights disease through cellular self-digestion","volume":"451","author":"Mizushima","year":"2008","journal-title":"Nature"},{"issue":"3","key":"bib30","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1007\/s00439-019-02031-7","article-title":"Autophagy in aging and longevity","volume":"139","author":"Wong","year":"2020","journal-title":"Hum Genet"},{"issue":"9","key":"bib31","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1038\/s41580-018-0033-y","article-title":"Autophagy as a promoter of longevity: insights from model organisms","volume":"19","author":"Hansen","year":"2018","journal-title":"Nat Rev Mol Cell Biol"},{"key":"bib32","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1007\/978-1-4939-2404-2","article-title":"Autophagy and aging","volume":"847","author":"Martinez-Lopez","year":"2015","journal-title":"Adv Exp Med Biol"},{"key":"bib33","doi-asserted-by":"publisher","first-page":"101967","DOI":"10.1016\/j.arr.2023.101967","article-title":"Autophagy-related proteins: Potential diagnostic and prognostic biomarkers of aging-related diseases","volume":"89","author":"Miceli","year":"2023","journal-title":"Ageing Res Rev"},{"issue":"3","key":"bib34","doi-asserted-by":"publisher","first-page":"489","DOI":"10.3390\/cells12030489","article-title":"Autophagy meets aging: an overview","volume":"12","author":"Picca","year":"2023","journal-title":"Cells"},{"issue":"1","key":"bib35","doi-asserted-by":"publisher","first-page":"e13753","DOI":"10.1111\/acel.13753","article-title":"Role of autophagy in aging: the good, the bad, and the ugly","volume":"22","author":"Tabibzadeh","year":"2023","journal-title":"Aging Cell"},{"issue":"16","key":"bib36","doi-asserted-by":"publisher","first-page":"1564","DOI":"10.1056\/NEJMra2022774","article-title":"Autophagy in human diseases","volume":"383","author":"Mizushima","year":"2020","journal-title":"N Engl J Med"},{"issue":"6","key":"bib37","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1016\/j.exer.2005.06.012","article-title":"Cell cycle status in human corneal endothelium","volume":"81","author":"Joyce","year":"2005","journal-title":"Exp Eye Res"},{"issue":"1","key":"bib38","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.exer.2011.08.014","article-title":"Proliferative capacity of corneal endothelial cells","volume":"95","author":"Joyce","year":"2012","journal-title":"Exp Eye Res"},{"issue":"3","key":"bib39","doi-asserted-by":"publisher","first-page":"1641","DOI":"10.1167\/iovs.10-6492","article-title":"Age-related gene response of human corneal endothelium to oxidative stress and DNA damage","volume":"52","author":"Joyce","year":"2011","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"suppl 1","key":"bib40","doi-asserted-by":"crossref","first-page":"S74","DOI":"10.1097\/ICO.0000000000001746","article-title":"Fuchs endothelial corneal dystrophy and mitochondria","volume":"37","author":"Miyai","year":"2018","journal-title":"Cornea"}],"container-title":["Investigative Ophthalmology &amp; Visual Science"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/iovs.arvojournals.org\/article.aspx?doi=10.1167\/iovs.67.5.71","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:32:24Z","timestamp":1791927144000},"score":1,"resource":{"primary":{"URL":"http:\/\/iovs.arvojournals.org\/article.aspx?doi=10.1167\/iovs.67.5.71"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,28]]},"references-count":40,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,5,1]]}},"URL":"https:\/\/doi.org\/10.1167\/iovs.67.5.71","relation":{},"ISSN":["1552-5783"],"issn-type":[{"value":"1552-5783","type":"print"}],"subject":[],"published":{"date-parts":[[2026,5,28]]}}}