Upregulation of miR-195 accelerates oxidative stress-induced retinal endothelial cell injury by targeting mitofusin 2 in diabetic rats

- miR-195 was upregulated in the diabetic rat retina and oxidative stressed HMRECs.
- miR-195 directly targeted the 3′- UTR of MFN2 mRNA.
- miR-195 regulated angiogenesis and vascular permeability by inhibiting the expression of MFN2.

This study was performed to investigate the oxidative stress-induced miRNA changes in relation to pathogenesis of diabetic retinopathy (DR) and to establish a functional link between miRNAs and oxidative stress-induced retinal endothelial cell injury. Our results demonstrated that oxidative stress could induce alterations of miRNA expression profile, including up-regulation of miR-195 in the diabetic retina or cultured HMRECs after exposed to H2O2 or HG (P < 0.05). Oxidative stress also resulted in a significant reduction of MFN2 expression in diabetic retina or HMRECs (P < 0.05). Overexpression of miR-195 reduced MFN2 protein levels, and induced tube formation and increased permeability of diabetic retinal vasculature. The luciferase reporter assay confirmed that miR-195 binds to the 3′ -untranslated region (3′-UTR) of MFN2 mRNA. This study suggested that miR-195 played a critical role in oxidative stress-induced retinal endothelial cell injury by targeting MFN2 in diabetic rats.