Up-regulation of P-glycoprotein expression by osmotic stress in rat sugar cataract

Abstract

P-glycoprotein (P-gp), a plasma membrane protein, is thought to function in the export of cytotoxic drugs and to act as a modulator of chloride channels that regulate cell volume in many cell types. P-gp has been shown to play a role in lens volume regulation and initiation of osmotic cataract. We investigated the lenticular expression levels of P-gp in galactose-fed rats, an experimental model of sugar cataract. P-gp was overexpressed in lenses from galactose-fed rats with cortical sugar cataract, and in rat lens epithelial cells cultured in high-glucose medium. However, application of aldose reductase (AR) inhibitor was able to reverse the changes in P-gp levels in the lenses of galactose-fed rats, confirming the role of AR and involvement of the polyol pathway in cataract formation. Our findings suggest that P-gp may be induced by AR over-expression and/or osmotic stress, thus playing a regulatory role in maintaining lenticular osmotic balance in sugar cataract.