title: The role of advanced glycation in the pathogenesis of diabetic retinopathy.
abstract: Retinopathy is one of the commonest microvascular complications of diabetes and is still the prevailing cause of registerable blindness in the working population of developed countries. The clinicopathology of microvascular lesions and the dysregulation of an array of biochemical pathways in the diabetic retina have been extensively studied, although the relative contribution of various biochemical sequelae of hyperglycaemia remains ill- defined. There is little doubt that the pathogenesis of this diabetic complication is highly complex and there is a pressing need to establish new therapeutic regimens that can effectively prevent or retard the initiation and progression of retinal microvascular cell dysfunction and death which is characteristic of the vasodegenerative stages of diabetic retinopathy. Among the several pathogenic mechanisms that may contribute to diabetic retinopathy are the formation and accumulation of advanced glycation endproducts (AGEs). AGEs can form on the amino groups of proteins, lipids, and DNA through a number of complex pathways, including nonenzymatic glycation by glucose and reaction with metabolic intermediates and reactive dicarbonyl intermediates. These reactions not only modify the structure and function of proteins, but also cause intramolecular and intermolecular cross-link formation. AGEs are known to accumulate in the diabetic retina where they may have important effects on retinal vascular cell function in vitro and in vivo. Evidence now points toward a pathogenic role for advanced glycation in the initiation and progression of diabetic retinopathy. This review will examine the basis of AGE-related pathology in the diabetic retina at cellular and molecular levels. It will also outline how recent strategies to inhibit AGE formation or limit their pathogenic influence during chronic diabetes may have an important role to play in the treatment of retinopathy.
authors.affiliation: Department of Ophthalmology, Queen's University of Belfast, Royal Victoria Hospital, Belfast BT12 6BA, Northern Ireland, UK.
authors.forename: Alan W
authors.initials: AW
authors.lastname: Stitt
mesh_terms: D000818:Animals; D048909:Diabetes Complications; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000378:metabolism; D003925:Diabetic Angiopathies / Q000473:pathology; D003930:Diabetic Retinopathy / Q000188:drug therapy / Q000209:etiology* / Q000473:pathology*; D004730:Endothelium, Vascular / Q000473:pathology; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D006801:Humans
chemical_list: D017127:Glycation End Products, Advanced