miR-429 negatively regulates the progression of hypoxia-induced retinal neovascularization by the HPSE-VEGF pathway

Abstract

Heparanase (HPSE) and vascular endothelial growth factor (VEGF) are believed to play a vital role in hypoxia-induced retinal neovascularization (RNV). HPSE is a target gene of miR-429. Our study aimed to investigate the effect of the miR-429-HPSE-VEGF pathway on hypoxia-induced RNV. The gene and protein expression of miR-429, HPSE and VEGF in human retinal endothelial cells and retinas was determined by real-time PCR and Western blot assays. The effects of miR-429 on human retinal endothelial cells and retinal neovascularization under hypoxia condition were verified by in vitro and in vivo experiments. First, we studied the effect of the miR-429-HPSE-VEGF pathway in HRECs under hypoxic conditions. HREC functions such as migration and tube formation were enhanced under hypoxic conditions. Overexpression of miR-429 in HRECs reversed these changes. Then, we investigated the effect of miR-429 on hypoxia-induced RNV in vivo. When miR-429 agomirs were injected into the vitreous cavity of mice with oxygen-induced retinopathy to overexpress miR-429, the mRNA and protein expression of VEGF was significantly reduced. In addition, indicators of retinal neovascularization, such as the retinal avascular area, and morphology of vessels, were reduced significantly in the miR-429 overexpression group. In this study, our data showed that miR-429 plays an important role by inhibiting the HPSE-VEGF pathway in hypoxia-induced retinopathy.

Keywords: Heparanase; Neovascularization; Retinopathy; VEGF; miR-429.