Prevention of Proliferative Diabetic Retinopathy and Cataract in SDT Rats with Aminoguanidine, an Anti-Advanced Glycation End Product Agent

Advanced glycation end products (AGEs) play important roles in the development of ocular complications in diabetes mellitus. Spontaneously Diabetic Torii (SDT) rats have marked hyperglycemia and severe ocular complications. We evaluated the effect of anti-AGE agents, aminoguanidine and pyridoxamine, and an antioxidant, probucol, on the development of diabetic retinopathy (DR) and cataract in SDT rats. Experiment 1 included five SDT rats treated with aminoguanidine, four SDT rats treated with probucol, and four untreated control SDT rats. After age 55 weeks, we evaluated DR by fluorescein angiomicroscopy and pathological study and cataract by biomicroscopy. Experiment 2 included six SDT rats treated with pyridoxamine, and six SDT rats and 10 non-diabetic normal Sprague-Dawley (SD) rats not treated with pyridoxamine. Retinopathy and cataract were evaluated as in experiment 1. Urinary pentosidine and Maillard reaction product X (MRX) levels were measured for 40 weeks in each group. Experiment 1: Mature cataracts and DR developed in all untreated SDT rats; aminoguanidine prevented cataracts and DR (p<0.05, vs untreated SDT rats). Probucol had no effect. Experiment 2: Mature cataracts developed in all untreated SDT rats (p<0.001 vs normal SD rats [0/10]) and DR developed in 67% (p<0.01, vs normal SD rats [0/10, 0%]). Pyridoxamine did not prevent cataracts (6/6, 100 ) or DR (4/6, 37%) (nonsignificant vs untreated SDT rats) in SDT rats. Urinary pentosidine levels were higher in untreated (0.12±0.07 μg/mg Cre) and pyridoxamine-treated (0.12±0.05 μg/mg Cre) SDT rats than normal SD rats (0.069±0.019 μg/mg Cre), but not significantly so. Urinary MRX levels were significantly (p<0.01) lower in normal SD rats (17.5±9.6 μg/mg Cre) compared with untreated SDT rats (163.0±107.0 μg/mg Cre); pyridoxamine had no effect (149.0±66.5 μg/mg Cre) (nonsignificant vs untreated SDT rats). Aminoguanidine but not pyridoxamine and probucol prevents DR and cataracts in SDT rats.