Impaired retinal angiogenesis in diabetes: Role of advanced glycation end products and galectin-3

Alan W. Stitt, Ciara McGoldrick, Aine Rice-McCaldin, David R. McCance, Josephine V. Glenn, Daniel K. Hsu, Fu-Tong Liu, Suzanne R. Thorpe, Tom A. Gardiner

Research output: Contribution to journalArticle

95 Scopus citations

Abstract

Suppression of angiogenesis during diabetes is a recognized phenomenon but is less appreciated within the context of diabetic retinopathy. The current study has investigated regulation of retinal angiogenesis by diabetic serum and determined if advanced glycation end products (AGEs) could modulate this response, possibly via AGE-receptor interactions. A novel in vitro model of retinal angiogenesis was developed and the ability of diabetic sera to regulate this process was quantified. AGE-modified serum albumin was prepared according to a range of protocols, and these were also analyzed along with neutralization of the AGE receptors galectin-3 and RAGE. Retinal ischemia and neovascularization were also studied in a murine model of oxygen-induced proliferative retinopathy (OIR) in wild-type and galectin-3 knockout mice (ga13-/-) after perfusion of preformed AGEs. Serum from nondiabetic patients showed significantly more angiogenic potential than diabetic serum (P < 0.0001) and within the diabetic group, poor glycemic control resulted in more AGEs but less angiogenic potential than tight control (P < 0.01). AGE-modified albumin caused a dose-dependent inhibition of angiogenesis (P < 0.001), and AGE receptor neutralization significantly reversed the AGE-mediated suppression of angiogenesis (P < 0.01). AGE-treated wild-type mice showed a significant increase in inner retinal ischemia and a reduction in neovascularization compared with non-AGE controls (P < 0.001). However, ablation of galectin-3 abolished the AGE-mediated increase in retinal ischemia and restored the neovascular response to that seen in controls. The data suggest a significant suppression of angiogenesis by the retinal microvasculature during diabetes and implicate AGEs and AGE-receptor interactions in its causation.

Original languageEnglish (US)
Pages (from-to)785-794
Number of pages10
JournalDiabetes
Volume54
Issue number3
DOIs
StatePublished - Mar 2005

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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    Stitt, A. W., McGoldrick, C., Rice-McCaldin, A., McCance, D. R., Glenn, J. V., Hsu, D. K., Liu, F-T., Thorpe, S. R., & Gardiner, T. A. (2005). Impaired retinal angiogenesis in diabetes: Role of advanced glycation end products and galectin-3. Diabetes, 54(3), 785-794. https://doi.org/10.2337/diabetes.54.3.785