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Advanced glycation: an important pathological event in diabetic and age related ocular disease
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  1. ALAN W STITT
  1. Department of Ophthalmology, The Queen's University of Belfast, The Royal Victoria Hospital, Belfast BT12 6BA, Northern Ireland, UK a.stitt@qub.ac.uk

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The formation of advanced glycation end products (AGEs) is a key pathophysiological event with links to a range of important human diseases. It is now clear that AGEs may act as mediators, not only of diabetic complications1 ,2 but also of widespread age related pathology such as Alzheimer's disease,3 decreased skin elasticity,4 ,5 male erectile dysfunction,6 ,7 pulmonary fibrosis,8 and atherosclerosis.9 ,10 Since many cells and tissues of the eye are profoundly influenced by both diabetes and ageing, it is fitting that advanced glycation is now receiving considerable attention as a possible modulator in important visual disorders. An increasing number of reports confirm widespread AGE accumulation at sites of known ocular pathology and demonstrate how these products mediate crosslinking of long lived molecules in the eye. Such studies also underscore the putative pathophysiological role of advanced glycation in ocular cell dysfunction in vitro and in vivo.

This article reviews some of the important effects that advanced glycation has on ocular tissues and the role that AGEs, and their specific receptors, have in the initiation and progression of sight threatening disorders such as diabetic retinopathy, glaucoma, cataract formation, and age related macular degeneration (AMD). This review also considers pharmacological strategies to prevent or neutralise the effects of AGEs and the recent development of potential therapies for AGE induced disease processes.

Biochemistry of AGE formation in biological systems

AGEs form via non-enzymatic condensation reactions between reducing sugars and ε-amino groups or N-terminal groups. These glycation modifications occur preferentially on lysine and arginine amino acids, although they can occur on free amine containing lipids and DNA and proceed spontaneously via a complex series of chemical rearrangements to yield reactive products with varying crosslinking, pigmentation, and fluorescence properties.11 Non-enzymatic glycation reactions were first described around the turn of the century …

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