{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T12:26:29Z","timestamp":1788956789059,"version":"build-2803163510"},"reference-count":54,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2022,9,23]],"date-time":"2022-09-23T00:00:00Z","timestamp":1663891200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005611","name":"University of Fukui","doi-asserted-by":"publisher","award":["LSI17102"],"award-info":[{"award-number":["LSI17102"]}],"id":[{"id":"10.13039\/501100005611","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Cataract causes vision loss and blindness due to formation of opacities of the lens. The regulatory mechanisms of cataract formation and progression remain unclear, and no effective drug treatments are clinically available. In the present study, we tested the effect of ataxia telangiectasia mutated (Atm) inhibitors using an<jats:italic>ex vivo<\/jats:italic>model in which rat lenses were cultured in galactose-containing medium to induce opacity formation. After lens opacities were induced by galactose, the lenses were further incubated with the Atm inhibitors AZD0156 or KU55933, which decreased lens opacity. Subsequently, we used microarray analysis to investigate the underlying molecular mechanisms of action, and extracted genes that were upregulated by galactose-induced opacity, but not by inhibitor treatment. Quantitative measurement of mRNA levels and subsequent STRING analysis revealed that a functional network consisting primarily of actin family and actin-binding proteins was upregulated by galactose treatment and downregulated by both Atm inhibitors. In particular,<jats:italic>Acta2<\/jats:italic>is a known marker of epithelial-mesenchymal transition (EMT) in epithelial cells, and other genes connected in this functional network (<jats:italic>Actn1<\/jats:italic>,<jats:italic>Tagln<\/jats:italic>,<jats:italic>Thbs1<\/jats:italic>, and<jats:italic>Angptl4<\/jats:italic>) also suggested involvement of EMT. Abnormal differentiation of lens epithelial cells via EMT could contribute to formation of opacities; therefore, suppression of these genes by Atm inhibition is a potential therapeutic target for reducing opacities and alleviating cataract-related visual impairment.<\/jats:p>","DOI":"10.1371\/journal.pone.0274735","type":"journal-article","created":{"date-parts":[[2022,9,23]],"date-time":"2022-09-23T18:23:32Z","timestamp":1663957412000},"page":"e0274735","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":13,"title":["Atm inhibition decreases lens opacity in a rat model of galactose-induced cataract"],"prefix":"10.1371","volume":"17","author":[{"given":"Masaya","family":"Nagaya","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumito","family":"Kanada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaru","family":"Takashima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiro","family":"Takamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaru","family":"Inatani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5563-0443","authenticated-orcid":true,"given":"Masaya","family":"Oki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,9,23]]},"reference":[{"issue":"6","key":"pone.0274735.ref001","doi-asserted-by":"crossref","first-page":"e339","DOI":"10.1016\/S2214-109X(13)70113-X","article-title":"Causes of vision loss worldwide, 1990\u20132010: a systematic analysis","volume":"1","author":"RR Bourne","year":"2013","journal-title":"Lancet Glob Health"},{"issue":"2","key":"pone.0274735.ref002","doi-asserted-by":"crossref","first-page":"103","DOI":"10.4103\/0301-4738.121141","article-title":"Etiopathogenesis of cataract: an appraisal","volume":"62","author":"VB Gupta","year":"2014","journal-title":"Indian J Ophthalmol"},{"issue":"1","key":"pone.0274735.ref003","doi-asserted-by":"crossref","first-page":"49","DOI":"10.3109\/09286589509071451","article-title":"Older-onset diabetes and lens opacities","volume":"2","author":"BE Klein","year":"1995","journal-title":"The Beaver Dam Eye Study. 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