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

H. P. Hammes, D. Strödter, A. Weiss, R. G. Bretzel, K. Federlin, M. Brownlee

Research output: Contribution to journalArticle

67 Scopus citations

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 languageEnglish (US)
Pages (from-to)656-660
Number of pages5
JournalDiabetologia
Volume38
Issue number6
DOIs
StatePublished - Jun 1 1995

Keywords

  • Diabetic retinopathy
  • aminoguanidine
  • glycation
  • islet transplantation
  • rat model
  • secondary intervention

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Fingerprint Dive into the research topics of 'Secondary intervention with aminoguanidine retards the progression of diabetic retinopathy in the rat model'. Together they form a unique fingerprint.

  • Cite this

    Hammes, H. P., Strödter, D., Weiss, A., Bretzel, R. G., Federlin, K., & Brownlee, M. (1995). Secondary intervention with aminoguanidine retards the progression of diabetic retinopathy in the rat model. Diabetologia, 38(6), 656-660. https://doi.org/10.1007/BF00401835