SECONDARY INTERVENTION WITH AMINOGUANIDINE RETARDS THE PROGRESSION OFDIABETIC-RETINOPATHY IN THE RAT MODEL

Primary prevention with aminoguanidine an inhibitor of advanced glycat ion end product (AGE) formation - has been successfully employed to pr event diabetic retinopathy in the rat. However, it is unknown whether inhibition of AGE formation is still effective in a secondary interven tion strategy. The present study addresses this question by comparing secondary intervention with aminoguanidine with syngeneic islet transp lantation in the rat model. After 6 months of diabetes, one group was treated with aminoguanidine (50 mg/100 ml drinking water; D-AG) while another group received syngeneic transplantation of collagenase-ficoll isolated islets by intraportal injection (Tx). After an additional 4 months, both groups were compared to a normal (NC 10) and diabetic (DC 10) control group. Retinal autofluorescence was increased 2.5-fold af ter 6 months and increased 3.7-fold after 10 months of diabetes (p < 0 .001). Aminoguanidine and islet Tx retarded the further accumulation o f autofluorescence equally (p < 0.001 vs DC 10), although the values w ere higher than those observed in DC at 6 months (p < 0.001). Diabetes was associated with a 2.7-fold increase in acellular capillaries afte r 6 months and a 4.1-fold increase after 10 months. Treatment with ami noguanidine or islet Tx reduced but did not completely attenuate the p rogression of vascular occlusion (p < 0.001 vs DC 10; D-AG vs DC 6, p < 0.05; Tx vs DC 6, p < 0.01), Both treatments reduced endothelial pro liferation (22.4% after 10 months; p < 0.001) and completely arrested pericyte dropout (40% after 10 months; p < 0.001). These data demonstr ate that aminoguanidine is as effective as islet transplantation in re tarding the progression of diabetic retinopathy in a secondary prevent ion setting.