The objective of the proposal is to study in greater detail the significance of intraocular generation of active species of oxygen and consequent oxidative stress in the pathogenesis of cataracts. In vitro studies will be conducted with rat lenses to determine the effect of various active species of oxygen on the physiology of the tissue in terms of ion and amino acid transport, as well as in terms of lipid peroxidation using the criteria of alkane liberation coupled with lipofuscin and malonaldehyde production. Emphasis will be laid on determining the role of OH in tissue damage through the use of appropriate radical scavengers. The ion transport measurements will be supplemented with the measurement of Na-K- ATPase activity of the tissue and LDH leakage by the tissue under oxidative stress. The studies will be conducted under photochemical as well as nonphotochemical systems. Since polyols are potent OH scavengers, studies will be conducted with lenses that are polyol deficient or enriched with polyols by incubating them with appropriate aldoses. Purified human and calf lens membranes will also be used to determined their susceptibility to active oxygen species. Prior to susceptibility studies, they will be examined for their basic fatty acid, phospholipids and lipofuscin components. Endogenous O2- and H2O2 production by the lens will also be measured by the tissue under oxidative stress. Possible induction of SOD and catalase will be studied under in vitro organ culture conditions as well in the intact animals exposed to hyperbaric oxygen. Further studies will be conducted to determine the function of lens and aqueous ascorbate in the maintenance of the HMP shunt. The role of ascorbate will also be evaluated in terms of its ability (DHA) to compete for NADPH involved in polyol synthesis and accumulation. Such a competition may perhaps have and effect on the rate of cataractogenesis induced by high sugar levels. In vivo studies will thus be conducted on the effect of ascorbate and other antioxidants against the development of sugar cataracts. Similar in vivo studies will be conducted on the effect of nutritional antioxidants on the progress of cataracts (senile) in emory mice. The monkey's aqueous humor will be analyzed for ascorbate and amino acid contents as a function of age.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY001292-15
Application #
3255844
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1978-09-01
Project End
1993-11-30
Budget Start
1990-12-01
Budget End
1991-11-30
Support Year
15
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of Maryland Baltimore
Department
Type
Schools of Medicine
DUNS #
003255213
City
Baltimore
State
MD
Country
United States
Zip Code
21201
Kronschläger, Martin; Löfgren, Stefan; Yu, Zhaohua et al. (2013) Caffeine eye drops protect against UV-B cataract. Exp Eye Res 113:26-31
Varma, Shambhu D; Kovtun, Svitlana; Hegde, Kavita R (2011) Role of ultraviolet irradiation and oxidative stress in cataract formation-medical prevention by nutritional antioxidants and metabolic agonists. Eye Contact Lens 37:233-45
Varma, Shambhu D; Hegde, Kavita R (2010) Kynurenine-induced photo oxidative damage to lens in vitro: protective effect of caffeine. Mol Cell Biochem 340:49-54
Varma, Shambhu D; Hegde, Kavita R (2010) Prevention of oxidative damage to lens by caffeine. J Ocul Pharmacol Ther 26:73-7
Hegde, K R; Varma, S D (2009) Electron impact mass spectroscopic studies on mouse retinal fatty acids: effect of diabetes. Ophthalmic Res 42:9-14
Hegde, Kavita R; Kovtun, Svitlana; Varma, Shambhu D (2007) Induction of ultraviolet cataracts in vitro: prevention by pyruvate. J Ocul Pharmacol Ther 23:492-502
Varma, S D; Hegde, K R; Kovtun, S (2006) Oxidative damage to lens in culture: reversibility by pyruvate and ethyl pyruvate. Ophthalmologica 220:52-7
Hegde, K R; Varma, S D (2005) Combination of glycemic and oxidative stress in lens: implications in augmentation of cataract formation in diabetes. Free Radic Res 39:513-7
Hegde, K R; Varma, S D (2005) Prevention of cataract by pyruvate in experimentally diabetic mice. Mol Cell Biochem 269:115-20
Hegde, K R; Varma, S D (2005) Cataracts in experimentally diabetic mouse: morphological and apoptotic changes. Diabetes Obes Metab 7:200-4

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