Does aldose reductase have a role in the development of the ocular complications of diabetes?
Diabetes mellitus has an effect on many organ systems including the eye, kidney and peripheral nerve. Many of these complications develop in animal models of diabetes, which has allowed some of the mechanisms of damage in target organs to be studied. Aldose reductase, an intracellular enzyme, converts glucose to sorbitol, and it is the intracellular accumulation of sorbitol which is thought to result in irreversible damage. In the diabetic eye the increased sorbitol accumulation in both the lens and the retina has been implicated in the pathogenesis of cataract and retinopathy, the major ocular complications of diabetes. In those experimental models which demonstrate characteristic diabetic complications, pharmacological inhibition of the enzyme aldose reductase has resulted in prevention of target organ damage. This paper summarises the experimental evidence upon which the clinical trials of aldose reductase inhibitors in diabetic patients have been initiated and the results of published drug trials in these patients.
Lightman
S
S
Institute of Ophthalmology, Moorfields Eye Hospital, London, UK.
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors / Q000502:physiology*; D000818:Animals; D002386:Cataract / Q000201:enzymology* / Q000473:pathology; D002986:Clinical Trials as Topic; D003316:Corneal Diseases / Q000201:enzymology*; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000201:enzymology; D003930:Diabetic Retinopathy / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use; D048289:Imidazolidines; D007908:Lens, Crystalline / Q000473:pathology; D010793:Phthalazines / Q000627:therapeutic use; D051381:Rats; D012171:Retinal Vessels / Q000648:ultrastructure
D007093:Imidazoles; D048289:Imidazolidines; D010793:Phthalazines; C042829:ponalrestat; D000449:Aldehyde Reductase; C026411:sorbinil