Aminoguanidine treatment inhibits the development of experimental diabetic retinopathy

Hans Peter Hammes, Sabine Martin, Konrad Federlin, Karl Geisen, Michael Brownlee

Research output: Contribution to journalArticle

455 Citations (Scopus)

Abstract

Retinal capillary closure induced by hyperglycemia is the principal pathophysiologic abnormality underlying diabetic retinopathy, but the mechanisms by which this induction occurs are not clear. Treatment of diabetic rats for 26 weeks with aminoguanidine, an inhibitor of advanced glycosylation product formation, prevented a 2.6-fold accumulation of these products at branching sites of precapillary arterioles where abnormal periodic acid/Schiff reagentpositive deposits also occurred. Aminoguanidine treatment completely prevented abnormal endothelial cell proliferation and significantly diminished pericyte dropout. After 75 weeks, untreated diabetic animals developed an 18.6-fold increase in the number of acellular capillaries and formed capillary microaneurysms, characteristic pathologic features of background diabetic retinopathy. In contrast, aminoguanidine-treated diabetic animals had only a 3.6-fold increase in acellular capillaries and no microaneurysms. These findings indicate that advanced glycosylation product accumulation contributes to the development of diabetic retinopathy and suggest that aminoguanidine may have future therapeutic use in this disorder.

Original languageEnglish (US)
Pages (from-to)11555-11558
Number of pages4
JournalProceedings of the National Academy of Sciences of the United States of America
Volume88
Issue number24
StatePublished - 1991

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Diabetic Retinopathy
Glycosylation
Pericytes
Periodic Acid
Arterioles
Therapeutic Uses
Hyperglycemia
Endothelial Cells
Cell Proliferation
pimagedine
Microaneurysm

Keywords

  • Endothelial cells
  • Glycation
  • Hyperglycemia
  • Microvascular disease
  • Pericytes

ASJC Scopus subject areas

  • General
  • Genetics

Cite this

Aminoguanidine treatment inhibits the development of experimental diabetic retinopathy. / Hammes, Hans Peter; Martin, Sabine; Federlin, Konrad; Geisen, Karl; Brownlee, Michael.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 88, No. 24, 1991, p. 11555-11558.

Research output: Contribution to journalArticle

Hammes, Hans Peter ; Martin, Sabine ; Federlin, Konrad ; Geisen, Karl ; Brownlee, Michael. / Aminoguanidine treatment inhibits the development of experimental diabetic retinopathy. In: Proceedings of the National Academy of Sciences of the United States of America. 1991 ; Vol. 88, No. 24. pp. 11555-11558.
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