Secondary intervention with aminoguanidine retards the progression of diabetic retinopathy in the rat model

Diabetologia. 1995 Jun;38(6):656-60. doi: 10.1007/BF00401835.


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).(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Arterioles / drug effects
  • Arterioles / pathology
  • Blood Glucose / metabolism
  • Body Weight / drug effects
  • Diabetes Mellitus, Experimental / physiopathology*
  • Diabetes Mellitus, Experimental / surgery
  • Diabetic Retinopathy / physiopathology
  • Diabetic Retinopathy / prevention & control*
  • Glycation End Products, Advanced / antagonists & inhibitors
  • Guanidines / administration & dosage
  • Guanidines / therapeutic use*
  • Islets of Langerhans Transplantation*
  • Male
  • Rats
  • Rats, Inbred Lew
  • Retinal Vessels / drug effects
  • Retinal Vessels / pathology
  • Transplantation, Isogeneic


  • Blood Glucose
  • Glycation End Products, Advanced
  • Guanidines
  • pimagedine