{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T22:26:33Z","timestamp":1793571993293,"version":"4.5.0"},"reference-count":35,"publisher":"SAGE Publications","issue":"10","license":[{"start":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T00:00:00Z","timestamp":1784160000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"Key Programme","award":["81570839"],"award-info":[{"award-number":["81570839"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Ocular Pharmacology and Therapeutics"],"published-print":{"date-parts":[[2026,12,1]]},"abstract":"<jats:sec>\n                    <jats:title>Purpose:<\/jats:title>\n                    <jats:p>Recurrent corneal erosion (RCE) is an ocular surface disease with poor epithelial\u2013stromal adhesion and limited therapies. This study aimed to elucidate the role of necroptosis, a pro-inflammatory form of programmed cell death, in the pathogenesis of corneal erosion.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      An\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      UVB injury model was established in human corneal epithelial cells (HCEpiCs), followed by unbiased LC\u2013MS\/MS proteomics and pathway enrichment analysis. In parallel, a UVB-induced corneal erosion model was generated in C57BL\/6 mice. To test therapeutic relevance, mice received a topical neutralizing anti-IFN-\u03b3 antibody or vehicle after injury. Corneal epithelial integrity and stromal architecture were assessed histologically, while activation of IFN-\u03b3\u2013JAK\/STAT signaling, RIPK1\/RIPK3\/MLKL necroptosis, DAMP release, NLRP3 inflammasome assembly, and IL-1\u03b2 maturation were examined using immunofluorescence, qRT-PCR, and Western blotting.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Proteomic profiling showed significant enrichment of necroptosis-related proteins following UVB exposure. UVB-treated corneal epithelium exhibited increased IFN-\u03b3 signaling and JAK\/STAT activation, accompanied by elevated expression and activation of RIPK1, RIPK3, and MLKL. Necroptosis was associated with increased release of DAMPs, heightened NLRP3 inflammasome activation, and increased maturation\/secretion of IL-1\u03b2.\n                      <jats:italic toggle=\"yes\">In vivo<\/jats:italic>\n                      , topical anti-IFN-\u03b3 treatment reduced corneal epithelial defects, improved epithelial\u2013stromal attachment, and decreased activation markers of the RIPK-MLKL and NLRP3\u2013IL-1\u03b2 pathways.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Our findings unveil a novel and critical pathogenic axis in corneal erosion, where IFN-\u03b3 signaling drives a necroptotic-inflammatory loop. This work provides a new molecular framework for understanding corneal epithelial injury and identifies the IFN-\u03b3-necroptosis axis as a promising therapeutic target for RCE.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/10807683261464756","type":"journal-article","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T05:16:14Z","timestamp":1784265374000},"page":"671-681","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Necroptosis Driven by JAK\/STAT-RIPK-MLKL Signaling Mediates Corneal Epithelial Erosion"],"prefix":"10.1177","volume":"42","author":[{"given":"Hongyi","family":"Shen","sequence":"first","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China."},{"name":"Department of Ophthalmology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 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