The relationship of glycaemic level to advanced glycation end-product (AGE) accumulation and retinal pathology in the spontaneous diabetic hamster

H. P. Hammes, B. Wellensiek, I. Klöting, E. Sickel, R. G. Bretzel, M. Brownlee

Research output: Contribution to journalArticle

55 Scopus citations

Abstract

To assess the relationship between glucose and advanced glycation end products (AGE) and the relationship between AGE and retinal changes in vivo, we studied the time course of retinopathy over 12 months in trypsin digest preparations and measured glycaemia and retinal AGE in spontaneous diabetic hamsters of mild (MD) and severe (SD) phenotypes. Blood glucose levels were elevated in MD (9.44 ± 0.76 mmol/l) and in SD (3 months: 24.3 ± 1.4 mmol/l; 12 months: 31.7 ± 0.8 mmol/l) over nondiabetic controls (NC: 7.15 ± 0.25 mmol/l; p < 0.05 or less vs MD; p < 0.001 vs SD). Similar relations were found for HbA1. Retinal AGE in mild diabetes was 405 ± 11.3 arbitrary units (AU) (NC 245 ± 7.7; p < 0.01) after 3 months and remained unchanged. A non- linear increase of AGE over time was found in severe hyperglycaemic hamsters (466 ± 21 AU after 3 months and 758 ± 21 AU after 12 months; p < 0.001 vs MD). Pericyte loss in mild diabetes progressed from -26% after 3 months to - 41% after 12 months (p < 0.001 vs NC). Whereas the initial pericyte loss in severely diabetic hamsters was identical to the mildly diabetic group, a higher degree of pericyte loss occurred after 12 months (-57%; p < 0.05 vs MD). Endothelial cell numbers remained unaffected by mild hyperglycaemia, but significantly increased over time in severe diabetes reaching 31.7% above controls after 12 months (p < 0.001 vs NC and MD). Microaneurysms were absent in all retinae examined. Acellular capillary segments were increased in mild diabetes (3.83 ± 0.31 per mm2 of retinal area) and severe diabetes (7.83 ± 0.73) over controls (1.0 ± 0.23). These data suggest that a threshold of glycaemia might exist above which AGE removal systems become saturated. Pericyte loss and acellular capillary formation are associated with mild increases in blood glucose and AGE levels while endothelial cell proliferation requires higher glucose and AGE levels.

Original languageEnglish (US)
Pages (from-to)165-170
Number of pages6
JournalDiabetologia
Volume41
Issue number2
DOIs
StatePublished - Mar 9 1998

Keywords

  • Advanced-glycation end- products
  • Chinese hamster
  • Diabetic retinopathy
  • Pericytes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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