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Mediators of Inflammation
Volume 2014 (2014), Article ID 746415, 10 pages
Research Article

The Proinflammatory Cytokine High-Mobility Group Box-1 Mediates Retinal Neuropathy Induced by Diabetes

1Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia
2Department of Ophthalmology, King Abdulaziz University Hospital, Old Airport Road, P.O. Box 245, Riyadh 11411, Saudi Arabia
3Laboratory of Histochemistry and Cytochemistry, University of Leuven, Leuven, Belgium

Received 15 July 2013; Revised 13 January 2014; Accepted 28 January 2014; Published 10 March 2014

Academic Editor: Charles J. Malemud

Copyright © 2014 Ahmed M. Abu El-Asrar et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


To test the hypothesis that increased expression of proinflammatory cytokine high-mobility group box-1 (HMGB1) in epiretinal membranes and vitreous fluid from patients with proliferative diabetic retinopathy and in retinas of diabetic rats plays a pathogenetic role in mediating diabetes-induced retinal neuropathy. Retinas of 1-month diabetic rats and HMGB1 intravitreally injected normal rats were studied using Western blot analysis, RT-PCR and glutamate assay. In addition, we studied the effect of the HMGB1 inhibitor glycyrrhizin on diabetes-induced biochemical changes in the retina. Diabetes and intravitreal injection of HMGB1 in normal rats induced significant upregulation of HMGB1 protein and mRNA, activated extracellular signal-regulated kinase 1 and 2 (ERK1/2), cleaved caspase-3 and glutamate; and significant downregulation of synaptophysin, tyrosine hydroxylase, glutamine synthetase, and glyoxalase 1. Constant glycyrrhizin intake from the onset of diabetes did not affect the metabolic status of the diabetic rats, but it significantly attenuated diabetes-induced upregulation of HMGB1 protein and mRNA, activated ERK1/2, cleaved caspase-3, and glutamate. In the glycyrrhizin-fed diabetic rats, the decrease in synaptophysin, tyrosine hydroxylase, and glyoxalase 1 caused by diabetes was significantly attenuated. These findings suggest that early retinal neuropathy of diabetes involves upregulated expression of HMGB1 and can be ameliorated by inhibition of HMGB1.