Effect Of Celecoxib On Expression Of VEGF In Retina Of Diabetic Rat

Neovascularization is pathology of the diabetic retina that lead to retinal detachment and blindness. These two vascular changes in diabetic retinopathy are associated with elevated retinal and vitreal vascular endothelial growth factor (VEGF), a potent inducer of vascular hyper-permeability and neovascularization. Macromolecules including VEGF neutralizing soluble receptor construct, VEGF neutralizing antibody, and VEGF-receptor chimeric proteins inhibited vascular hyperpermeability and/or neovascularization in diabetic rat and neovascular mouse models, suggesting that VEGF inhibition is useful in treating diabetic retinopathy. However, macromolecules suffer from poor stability and limited permeability , prompting the need to identify and develop small molecular drugs that can inhibit VEGF expression. To this end, we are investigating small molecular drugs capable of inhibiting VEGF expression.The production of prostaglandins, the products of cycloox- ygenase pathway that are capable of inducing VEGF expression, is increased by 40% in diabetic rat retinas, suggesting that cyclooxygenase plays a role in VEGF induction. There are two distinct isoforms of the enzyme cyclooxygenase—cyclooxygenase-1 and cyclooxygenase-2. While cyclooxygenase-1 is ubiquitous, cyclooxygenase-2 is induced under inflammatory conditions. Administration of high dose aspirin, a...