Mesenchymal marker expression is elevated in Müller cells exposed to high glucose and in animal models of diabetic retinopathy

• DOI: 10.18632/oncotarget.13945
• Publication Date: 2016-12-19T14:19:58Z
• Authors: Ti Zhou; Di Che; Yuqing Lan; Zhenzhen Fang; Jinye Xie; HaiJun Gong; ChaoYang Li; Juan Feng; Honghai Hong; Weiwei Qi; Caiqi Ma; Zhonghan Yang; WeiBin Cai; Jun Zhong; Jianxing Ma; Xia Yang; Guoquan Gao
• Keywords: Diabetic Retinopathy; Ependymoglial Cells; Cadherins; Actins; Streptozocin; Cell Line; Diabetes Mellitus, Experimental; Up-Regulation; 3. Good health; Mice; 03 medical and health sciences; Glucose; 0302 clinical medicine; Cell Movement; Animals; Humans; Vimentin; Snail Family Transcription Factors; Biomarkers; beta Catenin; Research Paper

Müller cells are retinal glial cells and exhibit a fibroblast-like phenotype and ability to migrate in diabetic retinopathy (DR). However, expression of mesenchymal markers, which promote fibrosis in various organs, has not been characterized in the diabetic retina. We examined changes in the expression of these markers in Müller cells exposed to high glucose and in animal models of diabetic retinopathy. High glucose conditions increased mesenchymal maker expression and migration in Müller cells. Snail, N-cadherin, Vimentin, β-catenin, and α-smooth muscle actin (α-SMA) levels were all dramatically increased in retinas from humans with diabetic retinopathy (DR) and from DR mouse models. In addition, Snail overexpression increased the expression of connective tissue growth factor (CTGF) and fibronectin, while Snail knockdown attenuated high glucose-induced increases in fibronectin and CTGF expression. These results demonstrate for the first time that mesenchymal markers are upregulated in retinas from a diabetic mouse model, and that Snail and N-cadherin levels are also increased in Müller cells exposed to high glucose. This suggests mesenchymal proteins may play a crucial role in the development of DR.