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Advanced glycation end products and diabetic retinopathy

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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.

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  1. University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, ON, K1Y 4W7, Canada

    Ross Milne

  2. Departments of Pathology and Laboratory Medicine, University of Ottawa, 501 Smyth Road, Ottawa, ON, K1H 8L6, Canada

    Ross Milne & Seymour Brownstein

  3. Department of Ophthalmology, University of Ottawa, 501 Smyth Road, Ottawa, ON, K1H 8L6, Canada

    Seymour Brownstein

  4. University of Ottawa, University of Ottawa Eye Institute and The Ottawa Hospital, 501 Smyth Road, Ottawa, ON, K1H 8L6, Canada

    Seymour Brownstein

  5. The Ottawa Hospital Research Institute, 725 Parkdale Avenue, Ottawa, ON, K1Y 4E9, Canada

    Seymour Brownstein

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Milne, R., Brownstein, S. Advanced glycation end products and diabetic retinopathy. Amino Acids 44, 1397–1407 (2013). https://doi.org/10.1007/s00726-011-1071-3

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