PPARγ agonists: Potential treatments for exudative age-related macular degeneration

Abstract

Choroidal neovascularization (CNV) characterizes the progression of exudative age-related macular degeneration (AMD) with the deterioration in the central vision. Vascular inflammation, and overproduction of inflammatory cytokines, growth factors and aberrant endothelial cell migration, initiate defective blood vessel proliferation in exudative AMD. CNV formation is initiated by the interplay between inflammation, the hallmark of exudative AMD, and the activation of WNT/β-catenin pathway. Upregulation of WNT/β-catenin pathway involves activation of PI3K/Akt pathway and then the Warburg effect to produce lactate. Lactate production generates VEGF expression and then participates to the initiation of CNV in exudative AMD. WNT/β-catenin pathway and PPARγ act in an opposite manner in several diseases. We focus this review on the interplay between PPARγ and canonical WNT/β-catenin pathway and the anti-inflammatory role of PPARγ in exudative AMD. In exudative AMD, PPARγ agonists downregulate inflammation and the WNT/β-catenin pathway. PPARγ agonists can appear as promising treatment against the initiation and the progression of CNV in exudative AMD.

Keywords: Canonical WNT/β-catenin pathway; Exudative AMD; Inflammation; PI3K/Akt pathway; PPARγ.