It is now known that human senile cataracts have undergone extensive oxidative alteration. This is evidenced by the accumulation of disulfide-rich high molecular weight protein aggregates in the cataractous lenses. The source of oxidation has not yet been definitively identified. Elevated H2O2 levels, however, have been discovered in the aqueous humor and the lens of human cataract patients. This suggests that H2O2 and its derivatives may be involved in the cataractogenesis and that the cataracts are incapable of detoxifying H2O2 efficiently. We propose to investigate: (1) whether there is an inherent weakness in the lens's H2O2 detoxifying mechanism, (2) whether there is an age-related loss of H2O2 detoxification, particularly the hexose monophosphate shunt-coupled system, (3) whether H2O2-induced damage can be identified, and (4) whether it is possible to augment the lens's resistance to H2O2. Both biochemical assays and nuclear magnetic resonance spectroscopy will be employed in this proposal. Successful completion of the proposed studies and demonstration of feasibility will enable us to develop anti-cataract agent(s) for the treatment of human senile cataracts.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY004424-03
Application #
3258822
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1983-07-01
Project End
1986-06-30
Budget Start
1985-07-01
Budget End
1986-06-30
Support Year
3
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Massachusetts Eye and Ear Infirmary
Department
Type
DUNS #
073825945
City
Boston
State
MA
Country
United States
Zip Code
Cheng, H M; Cheng, F Y; Xiong, H et al. (1996) The further metabolism of sorbitol-3-phosphate and fructose-3-phosphate in the mature rat lens. Ophthalmic Res 28:57-63
Cheng, H M; Xiong, J; Hirose, S et al. (1996) Nuclear magnetic resonance studies of sugar metabolism in the human infant lens. Ophthalmic Res 28 Suppl 2:5-10
Cheng, H M; Cheng, F Y; Tanaka, G H et al. (1995) Manipulating rat lens glucose metabolism with exogenous substrates. Exp Eye Res 61:479-86
Tsubota, K; Yoshida, M; Toda, T et al. (1993) Aldose reductase inhibition and the phosphorus-31 profile of the intact diabetic rat lens. Ophthalmic Res 25:393-9
Cheng, H M; Yoshida, A; Xiong, H et al. (1991) The effect of insulin and aldose reductase inhibition on the phosphate metabolism of streptozotocin-diabetic rat lens. Exp Eye Res 53:805-8
Cheng, H M; Xiong, J; Tanaka, G et al. (1991) Analysis of concurrent glucose consumption by the hexose monophosphate shunt, glycolysis, and the polyol pathway in the crystalline lens. Exp Eye Res 53:363-6
Cheng, H M; Xiong, H; Xiong, J et al. (1990) Metabolic studies of galactosemic cataract. Exp Eye Res 51:345-9
Cheng, H M; Xiong, H; Hirose, K (1989) Generation of alpha-L-glycerophosphate in the lens. Exp Eye Res 49:281-5
Xiong, H; Cheng, H M (1989) Aqueous/vitreous tonicity in ""sugar' cataracts. Ophthalmic Res 21:292-6
Tsubota, K; Krauss, J M; Kenyon, K R et al. (1989) Lens redox fluorometry: pyridine nucleotide fluorescence and analysis of diabetic lens. Exp Eye Res 49:321-34

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