Abnormalities of retinal metabolism in diabetes or experimental galactosemia VIII. Prevention by aminoguanidine

Purpose. Aminoguanidine has been found to inhibit the development of some r etinal lesions in diabetic rats and diabetic dogs, thereby raising a possib ility that the formation of glycation end products (AGEs) may be an essenti al step in the pathogenesis of the retinopathy. The purpose of this study i s to investigate the effect of aminoguanidine administration on other metab olic abnormalities which might be involved in the development of retinopath y in two models of the retinopathy, alloxan diabetes and experimental galac tosemia. Methods. Oxidative stress, nitric oxide (NO) and the activity of protein ki nase C (PKC, total activity) were measured in the retina of the rats experi mentally diabetic or galactosemic for 2 months. Effect of aminoguanidine ad ministration on the inhibition of hyperglycemia-induced retinal dysmetaboli sm was investigated. Results. Two months of diabetes or experimental galactosemia in rats result ed in elevation of retinal oxidative stress (increase in thiobarbituric aci d reactive substances, TBARS, and decrease in glutathione, GSH), NO, and PK C activity. Aminoguanidine supplementation (2.5 g aminoguanidine/kg rat die t) significantly inhibited each of these abnormalities in retinas of diabet ic rats and galactosemic rats, and did so without lowering the blood hexose levels of these animals. Conclusions. The ability of aminoguanidine to normalize the hyperglycemia-i nduced increases in retinal oxidative stress, NO and PKC in diabetic rats a nd galactose-fed rats suggests that these abnormalities may be inter-relate d in the retina, and that the biochemical mechanism by which aminoguanidine inhibits retinal microvascular disease in diabetes may be complex.