Aldose reductase as a regulator of ocular pathology: Mechanisms and therapeutic potential.

Abstract

Aldose reductase (AR), the rate-limiting enzyme of the polyol pathway, converts glucose to sorbitol using NADPH and becomes markedly overactive under hyperglycemic conditions. Its widespread expression in ocular tissues links AR to numerous eye disorders through sorbitol accumulation, microglial activation, NADPH depletion, oxidative stress, and increased formation of advanced glycation end products. These mechanisms contribute to the development of diabetic retinopathy, cataract, glaucoma, and other optic neuropathies, conditions that affect a large portion of the population and carry a substantial risk of progressing to vision loss if left untreated. The central involvement of AR in these processes has driven extensive development of aldose reductase inhibitors (ARIs), which reduce sorbitol buildup, oxidative stress, VEGF expression, and microglial activation. Thus, clarifying the functions of AR and therapeutically targeting this pathway remains essential for advancing strategies to prevent or slow the progression of ocular disease.