Ets2 Exacerbates Diabetic Retinopathy by Aggravating the Proliferation of Endothelial Cells and Inflammatory Response.

Abstract

Proliferative diabetic retinopathy (PDR), the most common type of diabetic retinopathy, is a main cause of visual and impairment blindness. Abnormal neovascularization, endothelial dysfunction, and vascular inflammation are important mechanisms for the development of PDR. Ets2 regulates angiogenesis-related genes and inflammation, however, the effect of Ets2 in PDR procession has not been clarified. Thus, this study is performed to investigate whether Ets2 exerts key functions in PDR. In this study, 10-week-old mice were used for establishing STZ-induced diabetic mice, and Ets2 expression was analyzed in retina tissues. Besides, newborn mice were applied to construct oxygen-induced retinopathy (OIR) models. The Ets2 expression, oxidative stress, and inflammation were detected in retina tissues. We found that Ets2 was highly expressed in retina tissues both in diabetic mice and OIR mice. Oxidative stress and inflammatory processes are two factors contributing to the pathogenesis of PDR. In retinal tissues of OIR mice, Ets2 knockdown inhibited expression of inflammatory mediators VEGFA, IL-6, and IL-8, and biomarkers of oxidative stress MCP-1, VCAM-1, and iNOS. ROS production was also inhibited by silencing Ets2. Ets2 deficiency inhibited endothelial cell proliferation in the retina. Furthermore, Ets2 knockdown contributed to suppressing the expression of angiogenesis-related genes VEGFA, JUNB, MMP-9, Tie2, Ang-2, and EphB4. Our study highlights that Ets2 accelerates PDR procession by promoting the proliferation of endothelial cells, oxidative stress, and inflammation, which provides a novel target against PDR.