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S.D. Varma, K.R. Hegde, S. Kovtun; Enhancement of Cataract Formation in Diabetes by Oxidative Stress Prevention by Pyruvate . Invest. Ophthalmol. Vis. Sci. 2005;46(13):3862.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Studies have been undertaken to investigate the hypothesis that the early maturation of senile cataracts in diabetics is attributable to the superimposition of the metabolic and oxidative stress induced by hyperglycemia on the existing age associated increase in the production of reactive oxygen species (ROS). Experiments were also extended to determine if such enhancement could be attenuated or prevented with pyruvate treatment. Methods: The hypothesis was investigated by culturing lenses from normal and diabetic rats, with or without menadione, and measuring their active cation transport activity. Results are expressed as the distribution ratio of the rubidium ions between the lens water and the medium (CL/CM), attained after four hrs of incubation. The metabolic and antioxidant status of the lens were assessed further by measuring ATP and GSH. Studies were also done with lenses isolated from diabetic rats treated with pyruvate known to inhibit oxidation as well as glycation of lens proteins and other macromolecules such as the nucleic acids. Results: CL/CM in the normal lens was 12 ±0.5, decreasing to 5.4±0.7 in presence of menadione (1mM). The corresponding ratios in the diabetic lenses were 5.5±0.05, and 3.1±0.4. In the pyruvate treated diabetic group, the corresponding ratios were 11.2±0.2 and 6.7±1. The results in this group were hence similar to that in the basal controls. The damaging effect of menadione, as reflected by the decrease in levels of ATP and GSH, was also more pronounced in the diabetic group not treated with pyruvate as compared to the pyruvate treated group. Conclusions: The results demonstrate that as compared to the normal lenses, the lenses of the diabetic animals are more susceptible to physiological damage by reactive oxygen species generated in vivo. This is evident by the lower level of active cation transport activity of the diabetic lenses and the corresponding decrease in the levels of ATP and GSH. Such an enhancement of the damaging process could be significantly prevented by administration of pyruvate to the diabetic animals. The greater susceptibility of the diabetic lenses to oxidative stress provides a reasonable explanation of the earlier maturation of cataracts in diabetics. Such enhanced susceptibility of the diabetic lenses to damage is amenable to attenuation by appropriate compounds effective in inhibiting glycation and scavenging ROS. Therefore the findings are also considered significant towards development of therapeutic measures against cataracts.
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