Issue 124 Item 13 Pyridoxamine Protects Against Diabetic Retinopathy

Pyridoxamine, an inhibitor of advanced glycation end products (AGEs), appears to protect against pathological changes in the retinas of diabetic rats and may be a new treatment for diabetic retinopathy. "This preclinical study is a demonstration of efficacy of pyridoxamine in preventing aspects of diabetic retinopathy in an experimental animal model," Dr. Alan Stitt from Royal Victoria Hospital, Belfast, Northern Ireland, told Reuters Health.

Dr. Stitt and colleagues compared the effects of pyridoxamine with the antioxidants vitamin E and R-alpha-lipoic acid in streptozotocin-induced diabetic rats, according to their report, published in the September issue of Diabetes.

The researchers gave the rats pyridoxamine 1g/L drinking water or 2,000 IU of vitamin E per kilogram diet or 0.05% per kilogram diet of R-alpha-lipoic acid.

"The approach we used looked at physical death of retinal capillaries during diabetes and some pathophysiological measures," Dr. Stitt said. The investigators examined the retinas of the animals after 29 days, looking for pathogenic changes and alterations in extracellular matrix gene expression and accumulation of immunoreactive carboxymethyl lysine from AGE and lipoxidation end products.

Compared with untreated rats, the pyridoxamine-treated animals were protected from capillary death, limited laminin protein up-regulation, extra-cellular matrix mRNA expression and an increase in carboxymethyl lysine in the retinal vessels.

"Interestingly, co-study of antioxidants did not have anywhere near the same effect in these animals," Dr. Stitt said. Rats treated with vitamin E or R-alpha-lipoic acid show no protection against retinal capillary closure and showed inconsistent effects on diabetes-related up-regulation of extracellular matrix mRNAs, the researchers found.

"This study shows that AGEs probably play an important role in diabetic retinopathy, although to be definitive about this there would need to be more studies conducted," Dr. Stitt said.

"This finding is important because diabetic retinopathy is a major cause of blindness in developed countries and there are no real therapeutic options for diabetic patients, beyond pan-retinal laser photocoagulation, which is very destructive of healthy retina and is only effective in the late stages," he added. "Further development of this therapeutic approach, or closely related strategies, have potential for preventing retinopathy in diabetic patients."

BioStratum, Inc., in Durham, North Carolina, is developing pyridoxamine as a drug called Pyridorin, Dr. Stitt noted. Diabetes 2002;51:2826-2832.