Pharmacological inhibition of diabetic retinopathy: aminoguanidine and aspirin.
Effects of aminoguanidine and aspirin on the development of retinopathy have been examined in 5-year studies of diabetic dogs. Either agent was administered daily in doses of 20-25 mg. kg(-1). day(-1). Because severity of hyperglycemia greatly influences development of the retinopathy, special effort was devoted to maintaining comparable glycemia in experimental and control groups. The retinal vasculature was isolated by the trypsin digest method, and retinopathy was assessed by light microscopy. Diabetes for 5 years resulted, as expected, in saccular capillary aneurysms, pericyte ghosts, acellular capillaries, retinal hemorrhages, and other lesions. Administration of aminoguanidine essentially prevented the retinopathy, significantly inhibiting 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 diabetes resulted in significantly increased levels of advanced glycation end products (AGEs) (namely, pentosidine in tail collagen and aorta, and Hb-AGE), aminoguanidine had no significant influence on these parameters of glycation. Nitration of a retinal protein was significantly increased in diabetes and inhibited by aminoguanidine. The biochemical mechanism by which aminoguanidine has inhibited retinopathy thus is not clear. Aminoguanidine (but not aspirin) inhibited a diabetes-induced defect in ulnar nerve conduction velocity, but neither agent was found to influence kidney structure or albumen excretion.
Kern
T S
TS
Departments of Medicine and Ophthalmology, Case Western Reserve University, Cleveland, Ohio 44106-4951, USA. tsk@po.cwru.edu
Engerman
R L
RL
D000418:Albumins / Q000378:metabolism; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001120:Arginine / Q000031:analogs & derivatives* / Q000378:metabolism; D001241:Aspirin / Q000627:therapeutic use*; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000188:drug therapy*; D003930:Diabetic Retinopathy / Q000517:prevention & control*; D004285:Dogs; D006442:Glycated Hemoglobin / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006029:Glycosuria / Q000378:metabolism; D006146:Guanidines / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects; D008239:Lysine / Q000031:analogs & derivatives* / Q000378:metabolism; D009431:Neural Conduction / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D011897:Random Allocation; D012171:Retinal Vessels / Q000187:drug effects; D014459:Ulnar Nerve / Q000187:drug effects
D000418:Albumins; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001120:Arginine; D001241:Aspirin; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D017127:Glycation End Products, Advanced; D006146:Guanidines; D008239:Lysine; C062187:pentosidine; C004479:pimagedine