Peroxisome proliferator-activated receptor alpha agonist suppresses neovascularization by reducing both vascular endothelial growth factor and angiopoietin-2 in corneal alkali burn

We investigated the effect of a peroxisome proliferator-activated receptor alpha (PPAR?alpha) agonist ophthalmic solution in wound healing using a rat corneal alkali burn model. After instillation of a selective agonist of PPAR?alpha, fenofibrate, onto the burned cornea, PPAR?alpha-positive cells were observed in vascular endothelial cells, and there was upregulation of mRNA of PPAR?alpha in corneal stroma. Fenofibrate suppressed expression of neutrophils and macrophages during the early phase, and development of neovascularization and myofibroblast generation during the late phase. Fenofibrate reduced not only mRNA expression of vascular endothelial growth factor-A but also angiopoietin-1 and angiopoietin-2. Furthermore, fenofibrate suppressed scar formation by reducing type III collagen expression. These data suggest that a PPAR?alpha agonist ophthalmic solution might be a new strategy for treating corneal wounds through not only anti-inflammatory effects but also by preventing neovascularization.