摘要
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.
Müller cells are macroglia and play many essentialroles as supporting cells in the retina. To respond topathological changes in diabetic retinopathy （DR）, amajor complication in the eye of diabetic patients,retinal Müller glia produce a high level of vascularendothelial growth factor （VEGF or VEGF-A）. As VEGFis expressed by multiple retinal cell-types and Müllerglia comprise only a small portion of cells in the retina,it has been a great challenge to reveal the function ofVEGF or other globally expressed proteins produced byMüller cells. With the development of conditional genetargeting tools, it is now possible to dissect the functionof Müller cell-derived VEGF in vivo . By using conditionalgene targeting approach, we demonstrate that Müllerglia are a major source of retinal VEGF in diabetic miceand Müller cell-derived VEGF plays a significant role inthe alteration of protein expression and peroxynitration,which leads to retinal inflammation, neovascularization,vascular leakage, and vascular lesion, key pathologicalchanges in DR. Therefore, Müller glia are a potentialcellular target for the treatment of DR, a leading causeof blindness.
基金
Supported by The NIH grants,Nos.GM104934,EY020900 and EY021725(NEI Core)
Chinese National Natural Science Foundation grant,No.81200699
grants from Presbyterian Health Foundation and Oklahoma Center for Adult Stem Cell Research and an endowment from Choctaw Nation(to Le YZ)
