Changes in the Gene Expression of Drug Metabolizing Enzymes during Cataractogenesis in Shumiya Cataract Rats

Abstract

The Shumiya cataract rat (SCR) is a hereditary cataract model in which lens opacity appears spontaneously in both the nuclear and perinuclear regions of 10-11 week old animals. The expression of drug metabolizing enzymes, including cytochrome P450 (CYP) and conjugation enzymes, was investigated in the ocular tissues of SCRs during cataractogenesis. Significantly high levels of gene expression were detected for CYP1A1, CYP2B2, CYP2C11 and CYP2E1 in normal lenses, whereas CYP1A1 and CYP2C11 were at lower levels in the cataractous lenses. The gene expression profiles of conjugation enzymes were also compared between normal and cataractous ocular tissues in which a moderate reduction in ST1A1 and ST1B1 expression, and an extensive loss of UGT1A1 expression, were observed in the SCR animals that had developed cataracts. In contrast, the elevated expression of the GSTA family of genes was evident in cataractous lenses. The reduced expression of several drug metabolizing enzymes in the cataractous ocular tissues might therefore be related to cataractogenesis via the accumulation of endogenous or exogenous toxic substances.