The role of VEGF in the development of diabetic retinopathy in dog

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When fed with galactose, dogs develop diabetes-like retinal capillary changes that include selective pericyte loss, microaneurysms and retinal hemorrhages. In addition, these early capillary changes can progress to the advanced proliferative stage with apparent new vessel formation. In this project, the potential role of vascular endothelial growth factor (VEGF) in the formation of new vessels of this particular dog model has been investigated. When cultured without any growth factors, cell survival of dog endothelial cells is significantly reduced. Addition of VEGF into the culture media protects these cells from cell death induced by growth factor starvation. At the same time, VEGF enhances tube-like formation of dog endothelial cells. Addition of VEGF also increases the expression of two VEGF receptors Flt-1 and KDR/Flk-1 and initiates the phosphorylation of the transcription factor Elk1. The tyrosine kinase inhibitor Genestein eliminates VEGF induced phosphorylation of Elk1 and cell growth. These data confirm that cell growth and tube formation of dog retinal capillary endothelial cells are stimulated by VEGF. VEFG also increases the expression of the receptors KDR and Flt-1 and activates the p44/42 MAP kinase pathway