Pharmacological inhibition of diabetic retinopathy - Aminoguanidine and aspirin

Effects of aminoguanidine and aspirin on the development of retinopathy hav e been examined in Ei-year studies of diabetic dogs. Either agent was admin istered daily in doses of 20-25 mg . kg(-1) . day(-1). Because severity of hyperglycemia greatly influences development of the retinopathy, special ef fort was devoted to maintaining comparable glycemia in experimental and con trol groups. The retinal vasculature was isolated by the trypsin digest met hod, and retinopathy was assessed by Light microscopy, Diabetes for 5 years resulted, as expected, in saccular capillary aneurysms, pericyte ghosts, a cellular capillaries, retinal hemorrhages, and other lesions. Administratio n of aminoguanidine essentially prevented the retinopathy, significantly in hibiting the development of retinal microaneurysms, acellular capillaries, and pericyte ghosts compared with diabetic controls. Aspirin significantly inhibited the development of retinal hemorrhages and acellular capillaries over the 5 years of study, but had less effect on other lesions. Although d iabetes resulted in significantly increased levels of advanced glycation en d products (AGEs) (namely, pentosidine in tail collagen and aorta, and Hb-A GE), aminoguanidine had no significant influence on these parameters of gly cation, Nitration of a retinal protein was significantly increased in diabe tes and inhibited by aminoguanidine, The biochemical mechanism by which ami noguanidine has inhibited retinopathy thus is not clear. Aminoguanidine (bu t not aspirin) inhibited a diabetes-induced defect in ulnar nerve conductio n velocity, but neither agent was found to influence kidney structure or al bumen excretion.