PMID- 23766563 OWN - NLM STAT- MEDLINE DCOM- 20131203 LR - 20211021 IS - 1466-1861 (Electronic) IS - 0962-9351 (Print) IS - 0962-9351 (Linking) VI - 2013 DP - 2013 TI - High-mobility group box-1 induces decreased brain-derived neurotrophic factor-mediated neuroprotection in the diabetic retina. PG - 863036 LID - 10.1155/2013/863036 [doi] LID - 863036 AB - To test the hypothesis that brain-derived neurotrophic factor-(BDNF-) mediated neuroprotection is reduced by high-mobility group box-1 (HMGB1) in diabetic retina, paired vitreous and serum samples from 46 proliferative diabetic retinopathy 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 TBARS. We also examined retinas of diabetic and HMGB1 intravitreally injected rats. The effect of the HMGB1 inhibitor glycyrrhizin on diabetes-induced changes in retinal BDNF expressions was studied. Western blot, ELISA, and TBARS assays were used. BDNF was not detected in vitreous samples. BDNF levels were significantly lower in serum samples from diabetic patients compared with nondiabetics, whereas HMGB1, sRAGE, sICAM-1, and TBARS levels were significantly higher in diabetic serum samples. MCP-1 levels did not differ significantly. There was significant inverse correlation between serum levels of BDNF and HMGB1. 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. Glycyrrhizin significantly attenuated diabetes-induced downregulation of BDNF. Our results suggest that HMGB1-induced downregulation of BDNF might be involved in pathogenesis of diabetic retinal neurodegeneration. FAU - Abu El-Asrar, Ahmed M AU - Abu El-Asrar AM AD - Department of Ophthalmology, College of Medicine, King Saud University, King Abdulaziz University Hospital, Old Airport Road, PO Box 245, Riyadh 11411, Saudi Arabia. abuasrar@ksu.edu.sa FAU - Nawaz, Mohd Imtiaz AU - Nawaz MI FAU - Siddiquei, Mohammad Mairaj AU - Siddiquei MM FAU - Al-Kharashi, Abdullah S AU - Al-Kharashi AS FAU - Kangave, Dustan AU - Kangave D FAU - Mohammad, Ghulam AU - Mohammad G LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130520 PL - United States TA - Mediators Inflamm JT - Mediators of inflammation JID - 9209001 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Chemokine CCL2) RN - 0 (HMGB1 Protein) RN - 126547-89-5 (Intercellular Adhesion Molecule-1) RN - 6FO62043WK (Glycyrrhizic Acid) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Animals MH - Blotting, Western MH - Brain-Derived Neurotrophic Factor/*blood MH - Chemokine CCL2/metabolism MH - Diabetic Retinopathy/*blood/drug therapy MH - Enzyme-Linked Immunosorbent Assay MH - Female MH - Glycyrrhizic Acid/therapeutic use MH - HMGB1 Protein/*pharmacology MH - Humans MH - Intercellular Adhesion Molecule-1/metabolism MH - Male MH - Middle Aged MH - Oxidative Stress/drug effects MH - Rats, Sprague-Dawley MH - Young Adult PMC - PMC3671668 EDAT- 2013/06/15 06:00 MHDA- 2013/12/16 06:00 PMCR- 2013/05/20 CRDT- 2013/06/15 06:00 PHST- 2013/04/15 00:00 [received] PHST- 2013/04/25 00:00 [accepted] PHST- 2013/06/15 06:00 [entrez] PHST- 2013/06/15 06:00 [pubmed] PHST- 2013/12/16 06:00 [medline] PHST- 2013/05/20 00:00 [pmc-release] AID - 10.1155/2013/863036 [doi] PST - ppublish SO - Mediators Inflamm. 2013;2013:863036. doi: 10.1155/2013/863036. Epub 2013 May 20.