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

Muller 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 Muller cells exposed to high glucose and in animal models of diabetic retinopathy. High glucose conditions increased mesenchymal maker expression and migration in Muller cells. Snail, N-cadherin, Vimentin, beta-catenin, and alpha-smooth muscle actin (alpha-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 Muller cells exposed to high glucose. This suggests mesenchymal proteins may play a crucial role in the development of DR.