Amino Acids

, Volume 44, Issue 6, pp 1397–1407

Advanced glycation end products and diabetic retinopathy

Review Article

DOI: 10.1007/s00726-011-1071-3

Cite this article as:
Milne, R. & Brownstein, S. Amino Acids (2013) 44: 1397. doi:10.1007/s00726-011-1071-3

Abstract

Retinopathy is a serious microvascular complication of diabetes and a major cause of blindness in young adults, worldwide. Early diabetic retinopathy is characterized by a loss of pericytes from retinal capillaries, the appearance of acellular capillaries and microaneurysms, and a breakdown of the blood–retinal barrier. In later stages, this can evolve into the proliferative phase in which there is neovascularization of the retina, which greatly increases the probability of vision loss. Advanced glycation end products (AGEs) which accumulate under hyperglycemic conditions are thought to play an important role in the pathogenesis of diabetic retinopathy. AGEs arise primarily by the modification of amine groups of proteins by reactive dicarbonyls such as methylglyoxal. Intracellular proteins including anti-oxidant enzymes, transcription factors and mitochondrial proteins are targets of dicarbonyl modification and this can modify their functional properties and thus compromise cellular physiology. Likewise, modification of extracellular proteins by dicarbonyls can impair cell adhesion and can generate ligands that can potentially bind to cell surface AGE receptors that activate pro-inflammatory signaling pathways. AGE inhibitors have been shown to provide protection in animal models of diabetic retinopathy and currently are being evaluated in clinical trials.

Keywords

Diabetic complications Advanced glycation endproducts Dicarbonyls Methylglyoxal Endothelial cells Pericytes 

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  1. 1.University of Ottawa Heart InstituteOttawaCanada
  2. 2.Departments of Pathology and Laboratory Medicine, University of OttawaOttawaCanada
  3. 3.Department of Ophthalmology, University of OttawaOttawaCanada
  4. 4.University of Ottawa, University of Ottawa Eye Institute and The Ottawa HospitalOttawaCanada
  5. 5.The Ottawa Hospital Research InstituteOttawaCanada

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