June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
High-mobility group box-1 induces decreased brain-derived neurotrophic factor-mediated neuroprotection in the diabetic retina
Author Affiliations & Notes
  • Mairaj Siddiquei
    Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia
  • Mohd Nawaz
    Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia
  • Ahmed Abu El-Asrar
    Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia
  • Footnotes
    Commercial Relationships Mairaj Siddiquei, None; Mohd Nawaz, None; Ahmed Abu El-Asrar, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 3239. doi:
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      Mairaj Siddiquei, Mohd Nawaz, Ahmed Abu El-Asrar; High-mobility group box-1 induces decreased brain-derived neurotrophic factor-mediated neuroprotection in the diabetic retina. Invest. Ophthalmol. Vis. Sci. 2013;54(15):3239.

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

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Abstract

Purpose: To test the hypothesis that brain-derived neurotrophic factor (BDNF)-mediated neuroprotection is reduced by high-mobility group box-1 (HMGB1) in the diabetic retina.

Methods: Paired vitreous and serum samples from 46 PDR and 34 nondiabetic patients were assayed for BDNF, HMGB1, soluble receptor for advanced glycation end products (sRAGE), soluble intercellular adhesion molecule-1 (sICAM-1), monocyte chemoattractant protein-1 (MCP-1) and thiobarbituric acid reactive substances (TBARS). In addition, we examined retinas of diabetic and HMGB1 intravitreally injected rats for the expression of BDNF, HMGB1, synaptophysin, TBARS and cleaved caspase-3. Retinas were dissected out, snap frozen and stored at -700C until analysis was done. Western blot analysis and enzyme-linked immunosorbent assay (ELISA) were used.

Results: BDNF was not detected in vitreous samples. BDNF levels were significantly lower in serum samples from patients with PDR compared with nondiabetic patients (p=0.015), whereas HMGB1, sRAGE, sICAM-1 and TBARS levels were significantly higher in PDR serum samples (p<0.001; p=0.008; p=0.019; p=0.011, respectively). MCP-1 levels did not differ significantly between patients with PDR and nondiabetic patients (p=0.836). There was a significant inverse correlation between serum levels of BDNF and HMGB1 (r=0.342; p=0.049). Diabetes and intravitreal administration of HMGB1 induced significant upregulation of the expression of HMGB1, TBARS and cleaved caspase-3, whereas the expression of BDNF and synaptophysin was significantly downregulated in rat retinas.

Conclusions: Our data suggest that diabetes-induced increased oxidative stress, down-regulation of BDNF and synaptophysin and upregulation of cleaved caspase-3 were also induced by HMGB1. Collectively, our present data suggest that blocking HMGB1 signaling pathways might be a novel therapeutic strategy for neuronal dysfunction in vision-threatening diabetic retinopathy.

Keywords: 499 diabetic retinopathy • 695 retinal degenerations: cell biology  
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