Study on Prevention of Cataract Development Contributing to Mitochondrial or Cell Membrane Damage

Abstract

It is important to elucidate mechanisms of lens opacification in order to development of anti-cataract drugs based on evidence. In this study, we show that the mechanisms for the lens opacification is different in three hereditary cataract model rats (UPLR, SCR and ICR). In addition, we investigated that the preventive effect of eye drops containing disulfiram on lens opacification. In UPLR, excessive NO cause damage to the mitochondrial genome, resulting in a decrease in ATP production and increase in Ca²⁺-ATPase activity. The decrease in ATP content cause the decrease in Ca²⁺-ATPase function resulting in the elevation in lens Ca²⁺ and opacification. In SCR and ICR, excessive NO cause an enhancement of lipid peroxidation resulting in the oxidative inhibition of Ca²⁺-ATPase. The decrease in Ca²⁺-ATPase activity cause the elevation in the level of lens Ca²⁺, thus leading to lens opacification. Furthermore, the instillation of eye drops containing a disulfiram and hydroxypropyl-β-cyclodextrin inclusion complex delays lens opacification in hereditary cataract model rats.