Functions Of Muller Cell-Derived Vascular Endothelial Growth Factor In Diabetic Retinopathy

Muller cells are macroglia and play many essential roles as supporting cells in the retina. To respond to pathological changes in diabetic retinopathy (DR), a major complication in the eye of diabetic patients, retinal Muller glia produce a high level of vascular endothelial growth factor (VEGF or VEGF-A). As VEGF is expressed by multiple retinal cell-types and Muller glia comprise only a small portion of cells in the retina, it has been a great challenge to reveal the function of VEGF or other globally expressed proteins produced by Muller cells. With the development of conditional gene targeting tools, it is now possible to dissect the function of Muller cell-derived VEGF in vivo. By using conditional gene targeting approach, we demonstrate that Muller glia are a major source of retinal VEGF in diabetic mice and Muller cell-derived VEGF plays a significant role in the alteration of protein expression and peroxynitration, which leads to retinal inflammation, neovascularization, vascular leakage, and vascular lesion, key pathological changes in DR. Therefore, Muller glia are a potential cellular target for the treatment of DR, a leading cause of blindness. (C) The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.