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The proinflammatory cytokine high‐mobility group box‐1 mediates retinal neuropathy induced by diabetes
Author(s) -
ABU EL ASRAR A,
SIDDIQUEI M,
NAWAZ M,
GEBOES K,
MOHAMMAD G
Publication year - 2014
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2014.4741.x
Subject(s) - glycyrrhizin , proinflammatory cytokine , diabetes mellitus , endocrinology , medicine , hmgb1 , downregulation and upregulation , diabetic retinopathy , retinal , chemistry , inflammation , biochemistry , ophthalmology , gene
Purpose 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. Methods 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. Results 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 hydoxylase and glyoxalase 1 caused by diabetes was significantly attenuated. Conclusion These findings suggest that early retinal neuropathy of diabetes involves upregulated expression of HMGB1 and can be ameliorated by inhibition of HMGB1.