This research group continues to conduct clinically related basic research using human and experimental animal tissues to elucidate the underlying pathogenic mechanisms of ocular diseases, including cataracts, keratopathy, and retinopathy with the ultimate aim of improving means of diagnosing, treating, and preventing ocular disorders. The main emphasis has been on the possible means of preventing ocular complications of diabetes. The areas of focus include: 1) demonstrating the involvement of the polyol pathway in diabetic ocular complications using the galactose-fed rat model; 2) defining how damage to the lens epithelium relates to cataracts; 3) elucidating the relative roles of polyol and non-enzymatic glycosylation (glycation) in cataracts; 4) demonstrating diabetic-like corneal sensitivity loss in galactosemic rats and its amelioration with aldose reductase inhibitors; 5) applying computerized morphometric analysis to preparations of isolated, intact retinal vasculatures; 6) determining the efficacious timing for intervening in diabetic retinopathy; 7) investigating the roles of growth factors in diabetes-induced angiogenesis; 8) utilizing a model of retinopathy of prematurity to study angiogenesis; and 9) evaluating agents that induce and inhibit retinal and vitreal angiogenesis. Since neovascularization plays a central role in the blinding stages of diabetic retinopathy, yet is poorly understood, we are now expanding our investigations to include elucidation of the possible mechanisms involved in new vessel growth. We will be examining the potential for artificially modulating retinal and vitreal neovascularization using various agents, including growth factors, such as vascular endothelial growth factor (VEGF), and inhibitors of the same.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Intramural Research (Z01)
Project #
1Z01EY000149-25
Application #
6106821
Study Section
Special Emphasis Panel (LMOD)
Project Start
Project End
Budget Start
Budget End
Support Year
25
Fiscal Year
1998
Total Cost
Indirect Cost
Name
U.S. National Eye Institute
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Sinha, D; Wyatt, M K; Sarra, R et al. (2001) A temperature-sensitive mutation of Crygs in the murine Opj cataract. J Biol Chem 276:9308-15
Piatigorsky, J; Kozmik, Z; Horwitz, J et al. (2000) Omega -crystallin of the scallop lens. A dimeric aldehyde dehydrogenase class 1/2 enzyme-crystallin. J Biol Chem 275:41064-73
Glover, J P; Jacot, J L; Basso, M D et al. (2000) Retinal capillary dilation: early diabetic-like retinopathy in the galactose-fed rat model. J Ocul Pharmacol Ther 16:167-72
Robison Jr, W G; Jacot, J L; Katz, M L et al. (2000) Retinal vascular changes induced by the oxidative stress of alpha-tocopherol deficiency contrasted with diabetic microangiopathy. J Ocul Pharmacol Ther 16:109-20
Grant, M B; Spoerri, P E; Player, D W et al. (2000) Plasminogen activator inhibitor (PAI)-1 overexpression in retinal microvessels of PAI-1 transgenic mice. Invest Ophthalmol Vis Sci 41:2296-302
Atwood, C S; Hovey, R C; Glover, J P et al. (2000) Progesterone induces side-branching of the ductal epithelium in the mammary glands of peripubertal mice. J Endocrinol 167:39-52