PPAR-alpha Ligands as Potential Therapeutic Agents for Wet Age-Related Macular Degeneration

The peroxisome proliferator-activated receptors (PPAR's) are members of the steroid/thyroid nuclear receptor, superfamily of transcription factors. There are currently three known PPAR subtypes, alpha, beta, and gamma. The PPARs are now recognized participants in a number of biological pathways some of which are implicated in the pathogenesis of age-related macular degeneration (AMD). These include immune modulation, lipid regulation, and oxidant/antioxidant pathways important to the onset and progression of "dry" AMD, and vascular endothelial growth factor (VEGF) mediated pathways that stimulate choroidal neovascularization (CNV), characteristic of "wet" AMD. PPAR-alpha is found in retina and also on vascular cells important to formation of CNV. At this time, however, relatively little is known about potential contributions of PPAR-alpha to the pathogenesis of dry and wet AMD. This review examines current literature for potential roles of PPAR-alpha in the pathogenesis and potential treatment of AMD with emphasis on prevention and treatment of wet AMD.