Published online Jun 10, 2015. doi: 10.4239/wjd.v6.i5.726
Peer-review started: September 18, 2014
First decision: January 8, 2015
Revised: February 21, 2015
Accepted: March 16, 2015
Article in press: March 18, 2015
Published online: June 10, 2015
Müller 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 Müller glia produce a high level of vascular endothelial growth factor (VEGF or VEGF-A). As VEGF is expressed by multiple retinal cell-types and Müller 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 Müller cells. With the development of conditional gene targeting tools, it is now possible to dissect the function of Müller cell-derived VEGF in vivo. By using conditional gene targeting approach, we demonstrate that Müller glia are a major source of retinal VEGF in diabetic mice and Müller 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, Müller glia are a potential cellular target for the treatment of DR, a leading cause of blindness.
Core tip: Diabetic retinopathy is a disorder of blood-retina barriers (BRBs) and neurons. Anti-vascular endothelial growth factor (VEGF) drugs are explored for treating BRB breakdown in the disease. As VEGF is also potentially beneficial, it is essential to understand the cellular and molecular mechanisms of VEGF action in the retina. Discussion is centered on the usefulness of conditional gene targeting mice in dissecting the function of globally expressed VEGF and in identifying significant roles for Müller glia-derived VEGF in diabetes-induced changes in protein expression/modification, inflammation, and BRB lesions and leakage.