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It has been established that there is about a 15% decrease in NADPH in the diabetic lens.35 The NADPH decrease could further impair the GSH/GSSG redox balance, as GSSG reduction by glutathione reductase requires NADPH as a cofactor.58, 59 NADPH is also involved in the biosynthesis of biological molecules such as fatty acids and nitric oxide, so its decrease or depletion should have deleterious effects on many anabolic pathways.60 Additionally, from a chemical point of view, the polyol pathway can also compete with glutathione reductase for NADPH,61, 62 leading to further impairment in glucose metabolism