Peroxisome Proliferated Activated Receptors (PPARs): Opportunities and Challenges for Ocular Therapy

Peroxisome proliferator-activated receptors (PPARs) are nuclear transcription factors. They exist in three isoforms (PPAR-α, PPAR-β/δ, and PPAR-Υ) in humans, but mainly PPAR-Υ, and they are expressed in retinal epithelial pigment. PPARs are involved in mediating numerous pathological implications in eye such as diabetic retinopathy (DR), choroidal neovascularization (CNV), glaucoma, diabetic macular edema, and other retinal diseases. Peroxisome proliferator-activated receptors are key players in various biological pathways like lipid degeneration, immune regulation, and reactive oxygen species regulation, regulation of vascular endothelial growth factor, matrixmetalloproteinase-9, and docosahexaenoic acid pathway. Based on evidence from clinical investigations, the drugs meant for PPARs could be promising candidates for intraocular therapy. Anti-VEGF therapy, including bevacizumab, ranibizumab, and aptamers (pegaptanib), has been approved for wet age-related macular degeneration (ARMD). Recently, researchers have explored the role of PPAR-γ in ocular pathophysiological processes and PPAR-γ agonists as novel adjuvants in the treatment of eye diseases. PPAR-γ exhibits potential benefits to improve or prevent various vision-threatening eye diseases such as age-related macular degeneration (ARMD), diabetic retinopathy (DR), keratitis, and optic neuropathy. However, PPAR-γ presents challenges and offers opportunities for ocular scientists to bring better outcomes.