Pathogenic Role of microRNA-21 in Diabetic Retinopathy Through Downregulation of PPARα

Fenofibrate, a specific agonist of peroxisome proliferator-activated receptor-α (PPARα), displays robust therapeutic effects on diabetic retinopathy (DR) in patients with type 2 diabetes. Our recent studies have shown that PPARα is downregulated in the diabetic retina, which contributes to the pathogenesis of DR. However, the mechanism for diabetes-induced downregulation of PPARα remains unknown. We investigated the role of ( ) in regulating PPARα in DR. was overexpressed, while PPARα levels were decreased in the retina of mice, a model of type 2 diabetes. Such alterations were also observed in palmitate-treated retinal endothelial cells. targeted PPARα by inhibiting its mRNA translation. Knockout of prevented the decrease of PPARα, alleviated microvascular damage, ameliorated inflammation, and reduced cell apoptosis in the retina of mice. Intravitreal injection of inhibitor attenuated PPARα downregulation and ameliorated retinal inflammation in mice. Further, retinal levels were increased, while PPARα levels were decreased in oxygen-induced retinopathy (OIR). Knockout of prevented PPARα downregulation and ameliorated retinal neovascularization and inflammation in OIR retinas. In conclusion, diabetes-induced overexpression of in the retina is at least partly responsible for PPARα downregulation in DR. Targeting may represent a novel therapeutic strategy for DR.