Diabetes-related adduct formation and retinopathy - PubMed (original) (raw)

Alan W Stitt et al. J Ocul Biol Dis Infor. 2011 Jun.

Abstract

The pathogenesis of diabetic retinopathy is complex, reflecting the array of systemic and tissue-specific metabolic abnormalities. A range of pathogenic pathways are directly linked to hyperglycaemia and dyslipidaemia, and the retina appears to be exquisitely sensitive to damage. Establishing the biochemical and molecular basis for this pathology remains an important research focus. This review concentrates on the formation of a range of protein adducts that form after exposure to modifying intermediates known to be elevated during diabetes. These so-called advanced glycation end products (AGEs) and advanced lipoxidation end products (ALEs) are thought to play an important role in the initiation and progression of diabetic retinopathy, and mechanisms leading to dysfunction and death of various retinal cells are becoming understood. Perspective is provided on AGE/ALE formation in the retina and the impact that such adducts have on retinal cell function. There will be emphasis placed on the role of the receptor for AGEs and how this may modulate retinal pathology, especially in relation to oxidative stress and inflammation. The review will conclude by discussion of strategies to inhibit AGE/ALE formation or harmful receptor interactions in order to prevent disease progression from the point of diabetes diagnosis to sight-threatening proliferative diabetic retinopathy and diabetic macular oedema.

Keywords: Advanced glycation; Diabetic retinopathy; Lipoxidation.

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Figures

Fig. 1

Fig. 1

The structures of lipoxidation-derived reactive carbonyl species and the principal advanced lipoxidation adducts formed following their reaction with proteins

Fig. 2

Fig. 2

FDP-lysine immunoreactivity (green channel) in retinal sections from non-diabetic and diabetic rats of 4-month disease duration. Cell nuclei are stained red by propidium iodide. In diabetes, prominent immunolabelling appeared in Müller glia end-feet and radial processes (arrows). GCL ganglion cell layer, INL inner nuclear layer, ONL outer nuclear layer. Scale bars = 50μm

Fig. 3

Fig. 3

Phase-contrast micrographs of cultured human MIO-M1 Müller glia exposed to increasing concentrations of FDP-lysine-modified human serum albumin (FDP-lysine-HSA). High concentrations of FDP-lysine-HSA (0.5 mg/mL) induce cell death. Scale bars = 100μm

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