Synergistic Effect of Glycemic and Oxidative Stress in Cataract Formation

Abstract

Abstract: : Purpose: Hyperglycemia is well known to cause an early depletion of lens glutathione. Since this tripeptide constitutes a primary antioxidant reserve, its loss could render the tissue more vulnerable to oxidative stress set out by normal oxyradical species generated in cellular respiration. The acceleration of senile cataract formation in diabetics may hence be attributable to a synergistic effect between the hyperglycemia induced biochemical changes and the direct oxyradical induced aberrations. The present investigations were conducted to study the possibility of this synergism using galactosemic rat model. Methods: Galactosemia was induced by maintaining rats on 50% galactose diet. The lenses isolated on the 9th day were incubated in the presence of air:CO₂ at 37degrees in Tyrode with or without menadione, the latter acting as a source of oxyradicals. Appropriate basal controls were also run. The medium also contained ⁸⁶RbCl in trace amounts. The physiological status of the lens was assessed by measuring its ability to conduct active transport of Rb⁺. The results were expressed as the distribution ratio attained at 5.5 hours. The levels of ATP and GSH, serving as indices of metabolic and oxidative damage, were also determined. Results: The distribution ratio attained in the normal lenses was ∼ 19.3±1. In the presence of menadione (oxidative stress), this was depressed to 8.6±0.5. The ratio in the galactosemic lenses (glycemic stress) was 7.4±0.2. In the latter group incubated with menadione (combined glycemic and oxidative stress) it decreased further to 3.6±0.1. The ATP levels in the normal lenses with or without menadione were 1675±150 and 2411±20 nanomoles/g respectively. However, in the galactosemic controls incubated without menadione, it reduced to 1215±100 nanomoles/g, with a further decrease to 859±75 nanomoles/g in those exposed to menadione. The levels of glutathione in the normal lenses incubated in the absence and presence of menadione were 5.4±0.2 and 2.4±0.2 µmoles/g respectively, with a further decrease to 1.1±0.01 and 0.59±0.01 µmoles/g in the galactosemic groups without and with menadione, respectively. Conclusions: The results suggest that the galactosemic lenses subjected to an oxidative stress undergo a significantly greater physiological damage to the cation transport function as well as depletions in the levels of ATP and GSH, as compared to the normal rat lenses exposed to oxidative stress alone. It is hypothesized that this synergism between a glycemic stress and followed by an oxidative stress could be involved in the acceleration of senile cataract formation in diabetics.

Keywords: cataract • diabetes • oxidation/oxidative or free radical damage