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 Citations (Scopus)

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 1995

Fingerprint

Diabetic Retinopathy
Isogeneic Transplantation
Islets of Langerhans Transplantation
Advanced Glycosylation End Products
Ficoll
Pericytes
Collagenases
Primary Prevention
Secondary Prevention
Drinking Water
Blood Vessels
pimagedine
Control Groups
Injections
Therapeutics

Keywords

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

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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

Secondary intervention with aminoguanidine retards the progression of diabetic retinopathy in the rat model. / Hammes, H. P.; Strödter, D.; Weiss, A.; Bretzel, R. G.; Federlin, K.; Brownlee, M.

In: Diabetologia, Vol. 38, No. 6, 06.1995, p. 656-660.

Research output: Contribution to journalArticle

Hammes, HP, Strödter, D, Weiss, A, Bretzel, RG, Federlin, K & Brownlee, M 1995, 'Secondary intervention with aminoguanidine retards the progression of diabetic retinopathy in the rat model', Diabetologia, vol. 38, no. 6, pp. 656-660. https://doi.org/10.1007/BF00401835
Hammes, H. P. ; Strödter, D. ; Weiss, A. ; Bretzel, R. G. ; Federlin, K. ; Brownlee, M. / Secondary intervention with aminoguanidine retards the progression of diabetic retinopathy in the rat model. In: Diabetologia. 1995 ; Vol. 38, No. 6. pp. 656-660.
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