Aldo-Keto Reductases in the Eye

Abstract

Aldose reductase (AKR1B1) is an NADPH-dependent aldo-keto reductase best known as the rate-limiting enzyme of the polyol pathway. Accelerated glucose metabolism through this pathway has been implicated in diabetic cataract and retinopathy. Some human tissues contain AKR1B1 as well as AKR1B10, a closely related member of the aldo-keto reductase gene superfamily. This opens the possibility that AKR1B10 may also contribute to diabetic complications. The goal of the current study was to characterize the expression profiles of AKR1B1 and AKR1B10 in the human eye. Using quantitative reverse transcriptase-PCR and immunohistochemical staining, we observed expression of both AKR genes in cornea, iris, ciliary body, lens, and retina. Expression of AKR1B1 was the highest in lens and retina, whereas AKR1B10 was the highest in cornea. Lenses from transgenic mice designed for overexpression of AKR1B10 were not significantly different from nontransgenic controls, although a significant number developed a focal defect in the anterior lens epithelium following 6 months of experimentally induced diabetes. However, lenses from AKR1B10 mice remained largely transparent following longterm diabetes. These results indicate that AKR1B1 and AKR1B10 may have different functional properties in the lens and suggest that AKR1B10 does not contribute to the pathogenesis of diabetic cataract in humans.