{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T11:31:32Z","timestamp":1786707092007,"version":"build-2736575974"},"reference-count":28,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007219","name":"Natural Science Foundation of Shanghai","doi-asserted-by":"publisher","award":["24ZR1408700"],"award-info":[{"award-number":["24ZR1408700"]}],"id":[{"id":"10.13039\/100007219","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Clinical Research Plan of Shanghai Hospital Development Center","award":["SHDC2024CRI076"],"award-info":[{"award-number":["SHDC2024CRI076"]}]},{"award":["SHDC2024CRI076"],"award-info":[{"award-number":["SHDC2024CRI076"]}],"id":[{"id":"https:\/\/ror.org\/02zrtve16","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Purpose: This study investigated the molecular mechanisms underlying blue light-induced corneal epithelial toxicity. Methods: C57BL\/6J mice were exposed to 460 nm blue light for 1, 2, or 4 weeks, whereas human corneal epithelial (HCE) cells were exposed for 15 or 30 min. RNA-sequencing with bioinformatic analysis identified p53 signaling and ferroptosis as key pathways. p53 knockdown using siRNA and pharmacological inhibition with pifithrin-\u03b1 (PFT-\u03b1) were employed to validate the mechanism in vitro and in vivo. Results: Blue light exposure caused time-dependent corneal epithelial disruption, reduced tear film stability, increased inflammatory cell infiltration, downregulated K12 expression, and upregulated K10 expression. Blue light induced cell death and G1-phase cell-cycle arrest in HCE cells. Ferroptosis hallmarks included intracellular ferrous iron (Fe2+) accumulation, reactive oxygen species (ROS) generation, decreased SLC7A11 and GPX4 expression, and increased COX2 expression. RNA sequencing revealed p53 pathway activation as a master regulator of ferroptosis. p53 knockdown reversed blue light-induced SLC7A11\/GPX4 suppression and COX2 upregulation. Topical PFT-\u03b1 administration attenuated corneal epithelial damage, restored K12 expression, suppressed K10 expression, and normalized ferroptosis markers in vivo. Conclusions: Blue light pollution triggers corneal epithelial ferroptosis through p53-mediated SLC7A11\/GPX4 axis suppression. Pharmacological inhibition of p53 represents a promising therapeutic strategy for blue light-associated dry eye.<\/jats:p>","DOI":"10.3390\/antiox15081014","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T10:39:01Z","timestamp":1786703941000},"page":"1014","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Blue Light Pollution and Ocular Surface Toxicity: p53-Mediated Ferroptosis in Corneal Epithelium Drives Dry Eye Pathogenesis"],"prefix":"10.3390","volume":"15","author":[{"given":"Lingyu","family":"Zhang","sequence":"first","affiliation":[{"name":"Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin 300384, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiwen","family":"Qian","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Huashan Hospital, Fudan University, Shanghai 200040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Huashan Hospital, Fudan University, Shanghai 200040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Huashan Hospital, Fudan University, Shanghai 200040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiliang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Huashan Hospital, Fudan University, Shanghai 200040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4495-6253","authenticated-orcid":false,"given":"Qingjian","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Huashan Hospital, Fudan University, Shanghai 200040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"118984","DOI":"10.1016\/j.ecoenv.2025.118984","article-title":"Blue light pollution induces dry eye by damaging conjunctival stem cells through cAMP-PKA-Pax6 signaling pathway","volume":"303","author":"Zhang","year":"2025","journal-title":"Ecotoxicol. 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