Comparison of the Mechanisms of Cataract Development Involving Differences in Ca^<2+> Regulation in Lenses among Three Hereditary Cataract Model Rats(Biochemistry)

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We previously found that the increases in Ca^<2+> content in the lenses of three hereditary cataract model rats, UPL rat (UPLR), Shumiya cataract rat (SCR) and Ihara cataract rat (ICR), are inhibited by aminoguanidine, a selective inhibitor of inducible nitric oxide synthase, and that the mechanisms of Ca^<2+> enhancement in these rat models differ. In this study, we compare the mechanisms for dysfunction in Ca^<2+> regulation in UPLR, SCR and ICR. Decreases in the activity of Ca^<2+>-ATPase were found in the lenses of SCR and ICR concurrent with cataract development. In contrast, the Ca^<2+>-ATPase activity in UPLR with opaque lenses was higher than in those with transparent lenses. On the other hand, ATP levels were markedly decreased in UPLR with opaque lenses. The expression of cytochrome c oxidase (CCO)-1 mRNA and CCO activity in UPLR lenses was found to decrease during cataract development. The nitric oxide (NO) and lipid peroxide levels were also increased in the lenses of UPLR, SCR and ICR with opaque lenses. In UPLR, excessive NO may cause damage to the mitochondrial genome, resulting in a decrease in ATP production and increase in Ca^<2+>-ATPase activity. The decrease in ATP content may cause the decrease in Ca^<2+>-ATPase function resulting in the elevation in lens Ca^<2+>. In SCR and ICR, excessive NO may cause an enhancement of lipid peroxidation resulting in the oxidative inhibition of Ca^<2+>-ATPase. The decrease in Ca^<2+>-ATPase activity may cause the elevation in the level of lens Ca^<2+>, thus leading to lens opacification. Our findings show that the Ca^<2+> contents in the cataractous lenses of all three model rats are increased, the mechanisms for this Ca^<2+> enhancement is different in each rat model.
社団法人日本薬学会の論文
2008-11-01

Comparison of the Mechanisms of Cataract Development Involving Differences in Ca^<2+> Regulation in Lenses among Three Hereditary Cataract Model Rats(Biochemistry)

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