Cell‐Free Fat Extract Promotes Cornea Epithelial Repair and Restores Neurodegeneration via an Anti‐Inflammation Pathway

Corneal injury and nerve degeneration are complex processes associated with various ocular pathologies, presenting significant challenges in ophthalmology. 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-enriched 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-free fat extract in ameliorating neurodegenerative changes in laser-induced corneal neurodegeneration and alkali burn-induced epithelial injury mouse models. The effects on nerve regeneration and epithelial cell proliferation were assessed through comprehensive histological, molecular, and functional analyses. RNA-sequencing 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-positive 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-1β and IL-18 through anti-inflammatory and anti-apoptotic pathways, with twice-daily 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-free nature and ease of administration, suggests significant potential for clinical translation in treating various ocular surface disorders. Further investigation into optimization and long-term outcomes will help advance this innovative treatment strategy.