Abstract

): The goal of this research is to clarify the pathogenesis of diabetic retinopathy and to provide a rational basis for developing improved means to inhibit the retinopathy. The proposed studies are based on our recent findings that aminoguanidine and aspirin both inhibit the development of retinopathy in diabetes. We will investigate the hypothesis that aminoguanidine and aspirin inhibit retinal pathology by inhibiting the same metabolic abnormalities in diabetes, especially excessive production of NO and of reactive dicarbonyls. The pathogenesis of diabetic retinopathy will be investigated by comparing effects of aminoguanidine and aspirin on retinal metabolism and histopathology to results observed using selective inhibitors of (1) dicarbonyl (and advanced glycation end product) production, (2) nitric oxide synthesis, and (3) poly (ADP-ribose) synthetase. Together, these selective inhibitors will investigate the roles of hyperglycemia-induced damage to DNA, caspase activation, and accelerated death of retinal capillary cells in the pathogenesis of diabetic retinopathy. Additional insight on how aminoguanidine inhibits retinopathy in diabetes will be gained by investigating why aminoguanidine fails to inhibit the morphologically similar retinopathy caused by galactose-feeding.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY000300-37
Application #
6696248
Study Section
Visual Sciences C Study Section (VISC)
Program Officer
Dudley, Peter A
Project Start
1977-12-01
Project End
2005-09-14
Budget Start
2004-01-01
Budget End
2005-09-14
Support Year
37
Fiscal Year
2004
Total Cost
$382,500
Indirect Cost

  Institution

Name
Case Western Reserve University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106

  Publications

Flückiger, Rudolf; Cocuzzi, Enzo; Nagaraj, Ram H et al. (2018) DAF in diabetic patients is subject to glycation/inactivation at its active site residues. Mol Immunol 93:246-252
Nahomi, Rooban B; Sampathkumar, Sruthi; Myers, Angela M et al. (2018) The Absence of Indoleamine 2,3-Dioxygenase Inhibits Retinal Capillary Degeneration in Diabetic Mice. Invest Ophthalmol Vis Sci 59:2042-2053
Tonade, Deoye; Liu, Haitao; Palczewski, Krzysztof et al. (2017) Photoreceptor cells produce inflammatory products that contribute to retinal vascular permeability in a mouse model of diabetes. Diabetologia 60:2111-2120
Kern, Timothy S (2017) Do photoreceptor cells cause the development of retinal vascular disease? Vision Res 139:65-71
Tonade, Deoye; Kern, Timothy S (2017) Diabetes of 5 years duration does not lead to photoreceptor degeneration in the canine non-tapetal inferior-nasal retina. Exp Eye Res 162:126-128
Tonade, Deoye; Liu, Haitao; Kern, Timothy S (2016) Photoreceptor Cells Produce Inflammatory Mediators That Contribute to Endothelial Cell Death in Diabetes. Invest Ophthalmol Vis Sci 57:4264-71
Zhang, Lingjun; Li, Yan; Payne, John et al. (2016) Presence of retinal pericyte-reactive autoantibodies in diabetic retinopathy patients. Sci Rep 6:20341
Liu, Haitao; Tang, Jie; Du, Yunpeng et al. (2016) Photoreceptor Cells Influence Retinal Vascular Degeneration in Mouse Models of Retinal Degeneration and Diabetes. Invest Ophthalmol Vis Sci 57:4272-81
Liu, Haitao; Tang, Jie; Du, Yunpeng et al. (2015) Retinylamine Benefits Early Diabetic Retinopathy in Mice. J Biol Chem 290:21568-79
Saliba, Alexandra; Du, Yunpeng; Liu, Haitao et al. (2015) Photobiomodulation Mitigates Diabetes-Induced Retinopathy by Direct and Indirect Mechanisms: Evidence from Intervention Studies in Pigmented Mice. PLoS One 10:e0139003

Showing the most recent 10 out of 95 publications