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Current therapeutic approaches often fail to fully restore corneal nerve function and tissue integrity after injury, highlighting the critical need for novel regenerative strategies. CEFFE, a bioactive compound\u2010enriched preparation derived from adipose tissue, has shown promising regenerative potential. However, its therapeutic efficacy in corneal repair remains unexplored. This study investigated the potential benefits of a cell\u2010free fat extract in ameliorating neurodegenerative changes in laser\u2010induced corneal neurodegeneration and alkali burn\u2010induced epithelial injury mouse models. The effects on nerve regeneration and epithelial cell proliferation were assessed through comprehensive histological, molecular, and functional analyses. RNA\u2010sequencing was used for mechanistic study. Our findings demonstrate that CEFFE treatment significantly enhanced corneal epithelial repair and regeneration, as evidenced by accelerated wound healing and increased Ki67\u2010positive proliferating cells. More importantly, CEFFE exhibited remarkable neuroprotective effects, preserving corneal nerve density and branching complexity while upregulating key neurotrophic factors. The therapeutic benefits were mediated by IL\u20101\u03b2 and IL\u201018 through anti\u2010inflammatory and anti\u2010apoptotic pathways, with twice\u2010daily administration showing superior efficacy. These findings establish CEFFE as a promising therapeutic approach for treating corneal injuries and neurodegeneration. The ability of CEFFE to simultaneously promote epithelial repair and nerve regeneration, combined with its cell\u2010free nature and ease of administration, suggests significant potential for clinical translation in treating various ocular surface disorders. Further investigation into optimization and long\u2010term outcomes will help advance this innovative treatment strategy.<\/jats:p>","DOI":"10.1096\/fj.202501327rr","type":"journal-article","created":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T04:15:36Z","timestamp":1761624936000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Cell\u2010Free Fat Extract Promotes Cornea Epithelial Repair and Restores Neurodegeneration via an Anti\u2010Inflammation Pathway"],"prefix":"10.1096","volume":"39","author":[{"given":"Yuanhua","family":"Xie","sequence":"first","affiliation":[{"name":"Department of Ophthalmology Xiangya Hospital, Central South University  Changsha China"},{"name":"Hunan Key Laboratory of Ophthalmology  Changsha China"},{"name":"National Clinical Research Center for Geriatric Disorders Xiangya Hospital, Central South University  Changsha 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