Methylglyoxal induces retinopathy‐type lesions in the absence of hyperglycemia: studies in a rat model

What is it about?

In this study, male Wistar rats were supplied with methylglyoxal (MG) by drinking water to evaluate whether damage to the neurovascular unit in diabetes depends on reactive metabolites such as MG, and to assess its impact on retinal gene expression. Systemic application of MG by drinking water increased retinal MG to levels comparable with diabetic animals and caused both (a) biochemical, (b) structural, and (c) functional damage in the retina, demonstrated by (a) MG-derived hydroimidazolone (MG-H1) modifications in the ganglion cell layer, inner nuclear layer and outer nuclear layer, and a moderate activation of the hexosamine pathway, (b) loss of pericytes and increased formation of acellular capillaries; and (c) a pan-retinal microglia activation and decreased function of bipolar cells. In addition, the retina upregulated the expression of potentially protective crystallins. We conclude that MG mimics important major aspects of diabetic retinopathy and plays a pathogenic role in microglial activation, vascular damage, and neuroretinal dysfunction. The substantial up-regulation of small HSPs suggests particular sensitivity of the retina towards reactive metabolites. Therapeutic enhancement of this inducible endogenous neuroprotective stress response system by HSP-inducing compounds could offer promising new concepts for the treatment of diabetic retinopathy.

Featured Image