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Pathogenesis of Diabetic Retinopathy and Diabetic Macular Edema and Enzyme Inhibition

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Abstract:

Diabetic retinopathy and diabetic macular edema (DME) remain important causes of visual loss worldwide despite the adoption of intensive glycemic control for the management of diabetes. Several interacting and mutually perpetuating abnormal biochemical systems, such as non-enzymatic glycation, protein kinase C (PKC) β activation, the polyol pathway, and oxidative stress, may be activated by sustained hyperglycemia in patients with diabetes. These abnormal systems may in turn influence several vasoactive factors, which are probably instrumental in the development of functional and morphological changes in the retina. Among the known vasoactive factors, vascular endothelial growth factor (VEGF), angiotensin II, and interleukin-6, are thought to be important in mediating the functional and structural alterations that occur in diabetic retinopathy and DME. Complex and interacting regulatory mechanisms, as well as enzyme inhibition, which are included advanced glycation end product inhibitor, PKC β inhibitor, aldose reductase inhibitor, antioxidant, angiotensin converting enzyme inhibitor, angiotensin II type 1 receptor blocker, and anti-VEGF, may modulate the ability of these molecules to produce biologically significant effects. Better understanding of these factors and their interactions should be of assistance in the development of new therapies for the treatment of diabetic retinopathy and DME.

Keywords: advanced glycation end products; diabetic macular edema; diabetic retinopathy; oxidative stress; polyol pathway; protein kinase cb; renin-angiotensin system; vascular endothelial growth factor

Document Type: Review Article

DOI: https://doi.org/10.2174/157340805774580411

Affiliations: Department of Ophthalmology, Diabetes Center, Tokyo Women's Medical University, 8- 1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan.

Publication date: 2005-11-01

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  • Current Enzyme Inhibition aims to publish all the latest and outstanding developments in enzyme inhibition studies with regards to the mechanisms of inhibitory processes of enzymes, recognition of active sites, and the discovery of agonists and antagonists, leading to the design and development of new drugs of significant therapeutic value. Each issue contains a series of timely, in-depth reviews written by leaders in the field, covering a range of enzymes that can be exploited for drug development. Current Enzyme Inhibition is an essential journal for every pharmaceutical and medicinal chemist who wishes to have up-to-date knowledge about each and every development in the study of enzyme inhibition.
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