[The oxidative stress in the cataract formation]

Abstract

The lens of the eye is an avascular tissue surrounded by fluids such as the aqueous humor and vitreous body, with one side facing toward the outside of the body. We investigated peroxidative reactions occurring in cataractous lenses, examining changes within the lens tissues as well as in the surrounding environment. 1. Peroxidative reactions in lenses. 1) Aging and peroxidative reactions. The activity of superoxide dismutase (SOD) began to decrease in the lenses of rats at six months of age. Moreover, the level of lipid peroxide increased significantly in the lenses of rats at 24 months of age. Lipoproteins became increasingly oxidized with age. The levels of Na+, K+, and Ca++, ions that are important to the maintenance of membrane function, also varied significantly with age. In the lenses of six-month-old Senescence Accelerated Mice (SAM), there was a marked decrease in the ability of scavenge active oxygen and a marked increase in the amount of lipid peroxide. In human lenses, the level of autofluorescence increased as the lens fiber structure changed with age. 2) Generation of free radicals inside the lens. We verified that HO. and ascorbic acid radicals were being generated inside cataractous lenses using electron spin resonance (ESR). 3) Changes in oxidation-related substances in cataractous lenses. Senile cataractous lenses and diabetic cataractous lenses were classified as four types, cortical, nuclear, posterior subcapsular, and mature. In cataractous lenses from all types of diabetic patients, the levels of glucose, glycated protein, and lipid peroxide were higher than in senile cataractous lenses. Among the four types of cataracts, the accumulation of peroxides was the greatest in the nuclear type both diabetic and senile cataractous lenses. 4) Transitional metals. Iron ions and copper ions existed in lens tissue. In particular, the subepithelial region of the lens stained strongly for copper ions. The increased level of copper ions in cataractous lenses is likely to be related to the increased peroxidation in this tissue. 5) Changes in membrane. Lowered levels of phospholipids and a higher degree of saturation of fatty acids were observed in senile cataractous lenses as compared with normal lenses. The increased saturation of fatty acids indicated that there was a damage to the membrane structure due to peroxidative reactions. The receptors for low density lipoprotein (LDL) were shown to exist on the epithelium of normal lenses. Acetyl-LDL, a denatured lipoprotein was incorporated into senile cataractous lenses but not into normal lenses, suggesting that the barrier function of the membrane deteriorates in cataractous lenses. Moreover, in diabetic cataractous lenses, the levels of very low density lipoprotein (VLDL) and LDL significantly increased. 2. Change in the environment surrounding the lens and peroxidative reactions. 1) Changes in the levels of oxidation-related substances in blood, aqueous humor, and vitreous body from diabetic patients: all had decreased levels of reduced glutathione and superoxide scavenging activity, and increased levels of lipid peroxide and glycated protein. This may have been due to a reduction in the anti-oxidative potential in the environment surrounding the lens due to the enhanced glycation. Changes in the level of oxidation related substances in the vitreous body in particular, will likely have a significant impact on the lens. 2) Changes in lenses as the surrounding environment deteriorates. Human lenses were cultured for three weeks under conditions similar to those found in vivo utilizing the culture system that we had originally designed and constructed. When protective activity against peroxidation was reduced, the amount of lipid peroxide increased significantly. In the presence of high levels of glucose, the levels of lipid peroxide increased and the amount and activity of SOD decreased. 3. Effects of changes in the external environment on peroxidative reactions.