WY-14 643, a Selective PPARα Agonist, Induces Proinflammatory and Proangiogenic Responses in Human Ocular Cells

Peroxisome proliferator-activated receptor alpha (PPAR alpha) agonism in ocular inflammation has not been thoroughly investigated. The objective of this investigation was to determine the effect of WY-14 643, a selective PPAR alpha agonist, on inflammatory cytokine release in human ocular cells. Stimulation of primary human corneal epithelial cells, keratocytes, and retinal endothelial cells with 1 to 10 ng/mL interleukin 1 beta (IL-1 beta) resulted in a significant increase in numerous inflammatory cytokines, including IL-6, IL-8, and tumor necrosis factor alpha (TNF-alpha); and dexamethasone was able to significantly inhibit these effects. However, WY-14 643 did not effectively block IL-1 beta-induced cytokine release in ocular cells; rather, significant increases in IL-1 beta-induced inflammatory cytokines were observed in these cells but not in aortic smooth muscle cells. WY-14 643 also significantly upregulated vascular endothelial growth factor (VEGF) expression in corneal epithelial cells and keratocytes. These studies demonstrate for the first time that PPAR alpha agonism may be proinflammatory and proangiogenic in a variety of ocular cells and suggest that therapeutic applications of such agents in ophthalmology may be limited.