{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T20:46:15Z","timestamp":1782938775103,"version":"3.54.5"},"reference-count":38,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:00:00Z","timestamp":1779235200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:00:00Z","timestamp":1779235200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82371098"],"award-info":[{"award-number":["82371098"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Age\u2010related cataract (ARC) is a severe vision\u2010impairing disorder primarily caused by oxidative stress\u2010induced senescence and apoptosis of lens epithelial cells (LECs). In this study, a sodium selenite\u2010induced oxidative stress cataract model in neonatal rats was established to simulate the pathological progression of ARC. We found that retinoic acid receptor\u2010related orphan receptor \u03b1 (RORA) exacerbates cellular senescence and oxidative damage by targeting prion protein (PRNP), and its small\u2010molecule inhibitor SR3335 exhibits therapeutic potential in regulating ARC progression. In\u00a0vitro experiments showed that inhibiting RORA significantly alleviated cellular senescence, enhanced the anti\u2010apoptotic capacity of LECs, and improved their resistance to oxidative stress, whereas activating RORA exerted opposite effects. In\u00a0vivo, intravitreal injection of recombinant PRNP protein was demonstrated to abrogate the protective effect of RORA silencing, thereby exacerbating the progression of ARC. Mechanistically, RNA sequencing and dual\u2010luciferase reporter assay revealed that RORA binds to its downstream target PRNP. RORA targets PRNP to regulate the p53\/p21\/Bax signaling pathway, thereby suppressing both cellular senescence and apoptosis. These findings highlight the critical role of the transcription factor RORA in ARC development by modulating oxidative stress injury, apoptosis, and senescence in LECs. The identification of PRNP as a downstream target of RORA may provide a novel dual\u2010target strategy for ARC treatment.<\/jats:p>","DOI":"10.1111\/acel.70547","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T20:34:48Z","timestamp":1779309288000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>RORA<\/scp>\n                    Targeting\n                    <scp>PRNP<\/scp>\n                    Modulates Age\u2010Related Cataract via Activation Oxidative Injury\u2010Induced Cellular Senescence and Apoptosis of Lens Epithelial Cells"],"prefix":"10.1111","volume":"25","author":[{"given":"Yue","family":"Zou","sequence":"first","affiliation":[{"name":"Department of Ophthalmology The First Affiliated Hospital of Chongqing Medical University  Chongqing China"},{"name":"Chongqing Key Laboratory of Prevention and Treatment on Major Blinding Diseases  Chongqing China"},{"name":"Chongqing Eye Institute  Chongqing China"},{"name":"Chongqing Branch (Municipality Division) of National Clinical Research Center for Ocular Diseases  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanqian","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology The First Affiliated Hospital of Chongqing Medical University  Chongqing China"},{"name":"Chongqing Key Laboratory of Prevention and Treatment on Major Blinding Diseases  Chongqing China"},{"name":"Chongqing Eye Institute  Chongqing China"},{"name":"Chongqing Branch (Municipality Division) of National Clinical Research Center for Ocular Diseases  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaojiao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology The First Affiliated Hospital of Chongqing Medical University  Chongqing China"},{"name":"Chongqing Key Laboratory of 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National Clinical Research Center for Ocular Diseases  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology The First Affiliated Hospital of Chongqing Medical University  Chongqing China"},{"name":"Chongqing Key Laboratory of Prevention and Treatment on Major Blinding Diseases  Chongqing China"},{"name":"Chongqing Eye Institute  Chongqing China"},{"name":"Chongqing Branch (Municipality Division) of National Clinical Research Center for Ocular Diseases  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Liang","sequence":"additional","affiliation":[{"name":"Changdu People's Hospital of Xizang  Xizang Changdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Kang","sequence":"additional","affiliation":[{"name":"Changdu People's Hospital of Xizang  Xizang Changdu 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Chongqing China"},{"name":"Chongqing Branch (Municipality Division) of National Clinical Research Center for Ocular Diseases  Chongqing China"},{"name":"Changdu People's Hospital of Xizang  Xizang Changdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shijie","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology The First Affiliated Hospital of Chongqing Medical University  Chongqing China"},{"name":"Chongqing Key Laboratory of Prevention and Treatment on Major Blinding Diseases  Chongqing China"},{"name":"Chongqing Eye Institute  Chongqing China"},{"name":"Chongqing Branch (Municipality Division) of National Clinical Research Center for Ocular Diseases  Chongqing 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