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Vasoactive Factors and Diabetic Retinopathy: Vascular Endothelial Growth Factor, Cycoloxygenase-2 and Nitric Oxide

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The pathogenetic agents involved in the development of diabetic retinopathy are diverse. In the setting of hyperglycaemia and retinal hypoxia a number of vasoactive factors may interact to promote pathology in a variety of cell types including the microvasculature, neurons and glia. Vascular endothelial growth factor (VEGF) is universally accepted as a primary factor in the regulation of vessel patency in vascular networks throughout the body and including the retina. There is considerable evidence that the VEGF system in disturbed early in diabetes and interacts with other pathways and vasoactive factors to stimulate breakdown of the blood retinal barrier (BRB) and eventually promote angiogenesis, the hallmark feature of proliferative diabetic retinopathy (PDR). There is a distinct relationship between VEGF and the prostaglandin-cyclooxygenase system. Prostaglandins influence retinal blood flow, are important in inflammation and are also pro-angiogenic. Recent evidence suggests that cyclooxygenase-2 (COX-2) modulates angiogenesis by interacting with the VEGF system. Like prostaglandins, nitric oxide (NO) is a vasodilator and is implicated in VEGF mediated vascular permeability and angiogenesis. Emerging evidence indicates that COX-2 also interacts with NO and that these two systems have reciprocal effects on each other. There is little doubt that the interactions between these three vasoactive systems are complex and requires further study in the context of retinal vascular permeability, angiogenesis and neurodegeneration. This review will explore experimental and clinical evidence that VEGF, COX-2 and NO promote retinal pathology in diabetes and other ischemic-induced retinopathies.
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Keywords: angiogenesis; cox-2; diabetic retinopathy; nitric oxide; vascular permeability; vegf

Document Type: Review Article

Affiliations: Department of Physiology, The University of Melbourne, Grattan St, Parkville, Victoria, Australia, 3010.

Publication date: October 1, 2004

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  • Current Pharmaceutical Design publishes timely in-depth reviews covering all aspects of current research in rational drug design. Each issue is devoted to a single major therapeutic area. A Guest Editor who is an acknowledged authority in a therapeutic field has solicits for each issue comprehensive and timely reviews from leading researchers in the pharmaceutical industry and academia.

    Each thematic issue of Current Pharmaceutical Design covers all subject areas of major importance to modern drug design, including: medicinal chemistry, pharmacology, drug targets and disease mechanism.
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