{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T01:27:14Z","timestamp":1793582834226,"version":"4.5.0"},"reference-count":68,"publisher":"Wiley","issue":"17","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2026,9,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Glaucoma is the leading cause of irreversible blindness worldwide, primarily driven by the progressive loss of retinal ganglion cells (RGCs) under pathological high intraocular pressure (ph\u2010IOP). Despite the established role of ferroptosis in RGC degeneration, specific molecular targets that can be used for clinical intervention still need to be optimized, and the slow onset of conventional gene therapy vectors is incompatible with the acute clinical course of glaucoma. Here, we integrate single\u2010cell RNA sequencing and spatial transcriptomics to profile the dynamic transcriptomic landscape of the rat retina across acute, subacute, and chronic stages of ph\u2010IOP injury. Through ferroptosis\u2010focused screening of an early\u2010activated RGC gene cluster, we identify the lipid metabolism regulator phosphatidylethanolamine\u2010binding protein 1 (PEBP1) as a candidate mediator of RGC ferroptosis. We demonstrate that\n                    <jats:italic>Pebp1<\/jats:italic>\n                    is specifically upregulated in injured RGCs with a trajectory mirroring ferroptosis pathway activation, and that AAV\u2010mediated\n                    <jats:italic>Pebp1<\/jats:italic>\n                    knockdown suppresses ferroptosis through the GPX4\/ACSL4 signaling axis, thereby preserving RGC survival, retinal structure, and visual function. To overcome the critical time\u2010window bottleneck\u2014the several weeks delay required for AAV\u2010mediated silencing versus the rapid, irreversible RGC loss in acute glaucoma\u2014we engineer Exosomes\u2010siPebp1, a mesenchymal stem cell\u2010derived exosome system loaded with siPebp1, which enables immediate single\u2010dose intervention post\u2010injury. This system exhibits efficient RGC uptake, prolonged intraocular retention, and robust target gene silencing, and, in a head\u2010to\u2010head comparison, significantly outperforms unloaded exosomes, liposomal formulations, and AAV vectors in RGC protection, without detectable acute systemic or local toxicity. Collectively, this study implicates\n                    <jats:italic>Pebp1<\/jats:italic>\n                    in ph\u2010IOP\u2010associated RGC ferroptosis and supports exosome\u2010mediated siRNA delivery as a rapid, cell\u2010free intervention strategy for acute glaucomatous injury.\n                  <\/jats:p>","DOI":"10.1096\/fj.202602807r","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T08:42:02Z","timestamp":1788424922000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["PEBP1 Regulates Ferroptosis in Acute Glaucoma: Targeted Therapy Using Engineered Exosomes"],"prefix":"10.1096","volume":"40","author":[{"given":"Yijia","family":"Huang","sequence":"first","affiliation":[{"name":"Shenzhen Eye Institute of Shenzhen Eye Hospital Jinan University  Shenzhen China"},{"name":"Shenzhen Eye Medical Center of Shenzhen Eye Hospital Southern Medical University  Shenzhen 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