Abstract
Primary prevention with aminoguanidine - an inhibitor of advanced glycation end product (AGE) formation - has been successfully employed to prevent diabetic retinopathy in the rat. However, it is unknown whether inhibition of AGE formation is still effective in a secondary intervention strategy. The present study addresses this question by comparing secondary intervention with aminoguanidine with syngeneic islet transplantation 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 after 6 months and increased 3.7-fold after 10 months of diabetes (p<0.001). Aminoguanidine and islet Tx retarded the further accumulation of autofluorescence equally (p<0.001 vs DC 10), although the values were higher than those observed in DC at 6 months (p<0.001). Diabetes was associated with a 2.7-fold increase in acellular capillaries after 6 months and a 4.1-fold increase after 10 months. Treatment with aminoguanidine or islet Tx reduced but did not completely attenuate the progression 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 proliferation (22.4% after 10 months; p<0.001) and completely arrested pericyte dropout (40% after 10 months; p<0.001). These data demonstrate that aminoguanidine is as effective as islet transplantation in retarding the progression of diabetic retinopathy in a secondary prevention setting.
Original language | English (US) |
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Pages (from-to) | 656-660 |
Number of pages | 5 |
Journal | Diabetologia |
Volume | 38 |
Issue number | 6 |
DOIs | |
State | Published - Jun 1995 |
Keywords
- Diabetic retinopathy
- aminoguanidine
- glycation
- islet transplantation
- rat model
- secondary intervention
ASJC Scopus subject areas
- Internal Medicine
- Endocrinology, Diabetes and Metabolism