{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T20:15:46Z","timestamp":1779912946658,"version":"3.53.1"},"reference-count":69,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2024,2,28]],"date-time":"2024-02-28T00:00:00Z","timestamp":1709078400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Cataract is an eye disease, in which the lens becomes opaque, causing vision loss and blindness. The detailed mechanism of cataract development has not been characterized, and effective drug therapies remain unavailable. Here, we investigated the effects of Hypoxia-inducible factor 1 (HIF-1) inhibitors using an <jats:italic>ex vivo<\/jats:italic> model, in which rat lenses were cultured in galactose-containing medium to induce opacity formation. We found that treatment with the HIF-1 inhibitors 2-Methoxyestradiol (2ME2), YC-1, and Bavachinin decreased lens opacity. Microarray analysis on 2ME2-treated samples, in which opacity was decreased, identified genes upregulated by galactose and downregulated by inhibitor treatment. Subsequent STRING analysis on genes that showed expression change by RT-qPCR identified two clusters. First cluster related to the cytoskeleton and epithelial-mesenchymal transition (EMT). Second cluster related to the oxidative stress, and apoptosis. ACTA2, a known marker for EMT, and TXNIP, a suppressor of cell proliferation and activator of apoptosis, were present in each cluster. Thus, suppression of EMT and apoptosis, as well as activation of cell proliferation, appear to underlie the decrease in lens opacity.<\/jats:p>","DOI":"10.1371\/journal.pone.0299145","type":"journal-article","created":{"date-parts":[[2024,2,28]],"date-time":"2024-02-28T18:31:06Z","timestamp":1709145066000},"page":"e0299145","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":8,"title":["HIF-1 inhibition reverses opacity in a rat model of galactose-induced cataract"],"prefix":"10.1371","volume":"19","author":[{"given":"Masaru","family":"Takashima","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaya","family":"Nagaya","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":[[2024,2,28]]},"reference":[{"issue":"10374","key":"pone.0299145.ref001","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/S0140-6736(22)01839-6","article-title":"Cataracts","volume":"401","author":"MV Cicinelli","year":"2023","journal-title":"Lancet"},{"issue":"43","key":"pone.0299145.ref002","first-page":"695","article-title":"Cataract surgery with implantation of an artificial lens","volume":"106","author":"T Kohnen","year":"2009","journal-title":"Dtsch Arztebl Int"},{"issue":"1","key":"pone.0299145.ref003","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1080\/08820538.2017.1353817","article-title":"Cataract Surgery in Patients with Diabetes: Management Strategies.","volume":"33","author":"SR Peterson","year":"2018","journal-title":"Semin Ophthalmol"},{"key":"pone.0299145.ref004","doi-asserted-by":"crossref","first-page":"8054073","DOI":"10.1155\/2018\/8054073","article-title":"Improving the Reliability and Utility of Streptozotocin-Induced Rat Diabetic Model.","volume":"2018","author":"Y Wang-Fischer","year":"2018","journal-title":"J Diabetes Res"},{"issue":"6","key":"pone.0299145.ref005","doi-asserted-by":"crossref","first-page":"e21593","DOI":"10.1096\/fj.202100353R","article-title":"Diabetic cataract in the Nile grass rat: A longitudinal phenotypic study of pathology formation","volume":"35","author":"E Ranaei Pirmardan","year":"2021","journal-title":"Faseb j"},{"issue":"4","key":"pone.0299145.ref006","doi-asserted-by":"crossref","first-page":"287","DOI":"10.4103\/0301-4738.81996","article-title":"Influence of galactose cataract on erythrocytic and lenticular glutathione metabolism in albino rats","volume":"59","author":"M Jyothi","year":"2011","journal-title":"Indian J Ophthalmol"},{"issue":"5","key":"pone.0299145.ref007","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1006\/exer.1996.0144","article-title":"High galactose levels in vitro and in vivo impair ascorbate regeneration and increase ascorbate-mediated glycation in cultured rat lens","volume":"63","author":"P Saxena","year":"1996","journal-title":"Exp Eye Res"},{"issue":"1","key":"pone.0299145.ref008","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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