MicroRNA-126 inhibits ischemia-induced retinal neovascularization via regulating angiogenic growth factors

To investigate the potential transcriptional regulation and signal pathway of a single microRNA in ischemia-induced retinal neovascularization (NV), we used oxygen-induced retinopathy (OIR) in establishing retinal NV model, and quantitative real-time reverse transcriptase PCR analyzing a microRNA (miR-126) alteration. The mice were treated with plasmid pCMV-MIR-126/liposome mixture intravitreal injection, using pCMV-MIR/liposome mixture as control. The expression levels of VEGF, IGF-2 and HIF-1 alpha, and the level changes of total and phosphorylated p38, ERK in retina from OIR mice were determined by western blot analysis. The effects of miR-126 on retinal NV in OIR mice were identified with fluoresecin angiography and H & E staining. No effect of miR-126 intravitreal injection on retinal vessels was performed with CD31 stained retinal sections. Our results showed that miR-126 was significantly decreased in retina from OIR mice. We confirmed that restoration of miR-126 in retina overcame the high levels of VEGF, IGF-2 and HIF-1 alpha through downregulating p38 and ERK signaling molecules in OIR model, and that miR-126 intravitreal injection reduced retinal NV in OIR model. These results suggest that miR-126 might play a potential transcriptional role in the pathogenesis in diabetic retinopathy. (C) 2011 Elsevier Inc. All rights reserved.