Aldose reductase inhibitor

Aldose reductase inhibitors are a class of drugs being studied as a way to prevent eye and nerve damage in people with diabetes.

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Mechanism

Their target, aldose reductase, is an enzyme that is normally present in many other parts of the body, and catalyzes one of the steps in the sorbitol(polyol) pathway that is responsible for fructose formation from glucose. Aldose reductase activity increases as glucose concentration rise in diabetes in those tissue that are not insulin sensitive, which includes the lenses, peripheral nerve and glomerulus. Sorbitol does not diffuse through cell membranes easily and therefore accumulates, causing osmotic damage which leads to retinopathy and neuropathy.

Examples

Examples of aldose reductase inhibitors include:

• epalrestat
• ranirestat^[1]

Diabetic cataract

Diabetic cataract formation follows an increase in sugars in the lens. The excess sugar within the lens is reduced by aldose reductase to its alcohol, but the lens capsule is relatively impermeable to sugar alcohols. Because of the excess sugar alcohol (polyol), the lens imbibes water, causing osmotic imbalance. Eventually, increased sodium and decreased potassium levels and decrease glutathione levels lead to cataract formation. Topical administration of aldose reductase inhibitors have been shown to prevent the cataract in rats.^[2]

References

1. ^ Várkonyi T, Kempler P (2007). "Diabetic neuropathy: new strategies for treatment". doi:10.1111/j.1463-1326.2007.00741.x. PMID 17593238.
2. ^ Newell, FW. Ophthalmology: Principles and Concepts, Fifth Edition. London: The CV Mosby Company, 1982, p. 332.