Functional role of PPARδ in corneal epithelial wound healing.

The peroxisome proliferator-activated receptor (PPAR) delta is involved in tissue repair. In this study, we investigated the functional role of PPAR delta in corneal epithelial wound healing. In an in vivo corneal wound-healing model, the changes of PPAR delta expression in corneal epithelia were examined by immunofluorescence microscopy, and the effect of topical administrations of a PPAR delta agonist on corneal wound healing was also evaluated. The inhibitory effect of a PPAR delta agonist on the cytokine-induced death of human corneal epithelial cells was evaluated using a DNA fragmentation assay kit. The changes of PPAR delta expression and epithelial cell death were also investigated using human corneoscleral tissues ex vivo. Our findings showed that PPAR delta expression was temporally up-regulated in corneal epithelial cells during experimental wound healing and that topical administration of a PPAR delta agonist significantly promoted the healing of experimental corneal epithelial wounds. In human corneal epithelial cells, up-regulation of PPAR delta and DNA fragmentation was demonstrated by stimulation with cytokines, and the DNA fragmentation was significantly inhibited by pretreatment with a PPAR delta agonist. By using human corneoscleral tissues ex vivo, PPAR delta was up-regulated in both healthy corneal epithelia (during re-epithelialization) and diseased corneal epithelia. Inflammatory stimulation induced corneal epithelial cell death was inhibited by pretreatment with a PPAR delta agonist. These results strongly suggest that PPAR delta is involved in the corneal epithelial wound healing. (Am J Pathol 2012, 180:583-594. DOL. 10.1016/j.ajpath.2011.10.006)