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ORIGINAL ARTICLE Ablation of 4E-BP1/2 Prevents Hyperglycemia-Mediated Induction of VEGF Expression in the Rodent Retina and in Müller Cells in Culture

By Tabitha L. Schrufer, David A. Antonetti, Nahum Sonenberg, Scot R. Kimball, Thomas W. Gardner and Leonard S. Jefferson

Abstract

OBJECTIVE—Vascular endothelial growth factor (VEGF) contributes to diabetic retinopathy, but control of its expression is not well understood. Here, we tested the hypothesis that hyperglycemia mediates induction of VEGF expression in a eukaryotic initiation factor 4E (eIF4E) binding protein (4E-BP) 1 and 2 dependent manner. RESEARCH DESIGN AND METHODS—The retina was harvested from control and type 1 diabetic rats and mice and analyzed for VEGF mRNA and protein expression as well as biomarkers of translational control mechanisms. Similar analyses were performed in Müller cell cultures exposed to hyperglycemic conditions. The effect of 4E-BP1 and 4E-BP2 gene deletion on VEGF expression was examined in mice and in mouse embryo fibroblasts (MEFs). RESULTS—Whereas VEGF mRNA in the retina remained constant

Year: 2013
OAI identifier: oai:CiteSeerX.psu:10.1.1.352.774
Provided by: CiteSeerX
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