NITRIC OXIDE IN THE PATHOGENESIS OF DIABETIC RETINOPATHY

Project: Research project

Description

DESCRIPTION: Diabetic retinopathy is the leading cause of blindness in adults in the U.S.A. Preliminary studies led to the hypothesis that high glucose generates chronically increased NO levels that results in endothelial cell dysfunction and impaired blood-retinal integrity responsible for diabetic retinopathy. Three types of studies will test the hypothesis. 1. Changes in NO synthase (NOS) and endothelial permeability will be characterized in a spontaneous diabetic rat model and in a galactose-induced mouse model of retinopathy. Galactose-fed mice with specific NOS deficiencies for two isoforms will also be characterized. Techniques include quantitative RT-PCR, immunocytochemistry, and magnetic resonance imaging. 2. Mechanisms for NO action will be probed in cultured retinal endothelial cells from wild-type mice and ENOS and INOS deficient mice. Interactions of glucose, IGF-1, VEGF, and cytokines will be defined with the in vitro approach Several techniques are utilized to evaluate endothelial permeability and NO activity. 3. Vector-mediated gene expression will test the hypothesis that NOS overexpression contributes to disease progression. Ribozymes designed to decrease NOS isoform expression in the rat model of spontaneous diabetes will be used to test the corollary that excess NOS expression in diabetes potentiates BRB dysfunction.
StatusFinished
Effective start/end date9/30/985/31/16

Funding

  • National Institutes of Health: $418,491.00
  • National Institutes of Health: $406,994.00
  • National Institutes of Health: $363,750.00
  • National Institutes of Health: $431,410.00
  • National Institutes of Health: $363,021.00
  • National Institutes of Health: $365,756.00
  • National Institutes of Health: $290,358.00
  • National Institutes of Health: $410,650.00
  • National Institutes of Health: $362,500.00
  • National Institutes of Health: $347,437.00
  • National Institutes of Health: $179,338.00
  • National Institutes of Health
  • National Institutes of Health: $362,479.00
  • National Institutes of Health: $362,500.00
  • National Institutes of Health
  • National Institutes of Health: $368,011.00
  • National Institutes of Health: $347,437.00

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Diabetic Retinopathy
Endothelial Cells
Nitric Oxide Synthase
Nitric Oxide
Retinal Vessels
Reactive Oxygen Species
Retinal Artery
Population
Blood Vessels
Oxidation-Reduction
Free Radicals
Blindness
Peroxynitrous Acid
Catalytic RNA
Bone Marrow
Oxygen
Protein Isoforms
Glucose
Galactose
Cell Movement

ASJC

  • Medicine(all)