April 2014
Volume 55, Issue 13
ARVO Annual Meeting Abstract  |   April 2014
High-mobility group box-1 modulates the expression of inflammatory and angiogenic signaling pathways in diabetic retina
Author Affiliations & Notes
  • Ghulam Mohammad
    Ophthalmology, King Saud University, Riyadh, Saudi Arabia
  • Footnotes
    Commercial Relationships Ghulam Mohammad, None
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    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 1036. doi:
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      Ghulam Mohammad; High-mobility group box-1 modulates the expression of inflammatory and angiogenic signaling pathways in diabetic retina. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1036.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: The expression of high-mobility group box-1 (HMGB1) is upregulated in epiretinal membranes and vitreous fluid from patients with proliferative diabetic retinopathy and in the diabetic retina. HMGB1 mediates inflammation, breakdown of blood-retinal barrier and apoptosis in the diabetic retina. Here, we investigated inflammatory and angiogenic signaling pathways activated by HMGB1 in the diabetic retina

Methods: The retinas from 1-month diabetic rats and from normal rats intravitreally injected with HMGB1 were studied using RT-PCR, Western blot analysis and co-immunoprecipitation. We also 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 the mRNA levels of HMGB1 and CXCR4 and the protein levels of hypoxia-inducible factor-1, early growth response -1, activated extracellular signal-regulated kinase 1 and 2, tyrosine kinase 2 and the CXCL12/CXCR4 chemokine axis. Constant glycyrrhizin intake from the onset of diabetes did not affect the metabolic status of the diabetic rats, but it restored these increased mediators to control values. Co-immunoprecipitation studies showed that diabetes increased the interaction between CXCL12 and CXCR4 and between HMGB1 and receptor for advanced glycation end products (RAGE), but not between HMGB1 and CXCL12/CXCR4 chemokine axis.

Conclusions: HMGB1 activates inflammatory and angiogenic signaling pathways in the diabetic retina mediated by RAGE.

Keywords: 499 diabetic retinopathy • 490 cytokines/chemokines • 557 inflammation  

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