Document Detail


The high-mobility group box-1 nuclear factor mediates retinal injury after ischemia reperfusion.
MedLine Citation:
PMID:  21828158     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: High-mobility group protein B1 (Hmgb1) is released from necrotic cells and induces an inflammatory response. Although Hmgb1 has been implicated in ischemia/reperfusion (IR) injury of the brain, its role in IR injury of the retina remains unclear. Here, the authors provide evidence that Hmgb1 contributes to retinal damage after IR.
METHODS: Retinal IR injury was induced by unilateral elevation of intraocular pressure and the level of Hmgb1 in vitreous humor was analyzed 24 hours after reperfusion. To test the functional significance of Hmgb1 release, ischemic or normal retinas were treated with the neutralizing anti-Hmgb1 antibody or recombinant Hmgb1 protein respectively. To elucidate in which cell type Hmgb1 exerts its effect, primary retinal ganglion cell (RGC) cultures and glia RGC cocultures were treated with Hmgb1. To clarify the downstream signaling pathways involved in Hmgb1-induced effects in the ischemic retina, receptor for advanced glycation end products (Rage)-deficient mice (RageKO) were used.
RESULTS: Hmgb1 is accumulated in the vitreous humor 24 hours after IR. Inhibition of Hmgb1 activity with neutralizing antibody significantly decreased retinal damage after IR, whereas treatment of retinas or retinal cells with Hmgb1 induced a loss of RGCs. The analysis of RageKO versus wild-type mice showed significantly reduced expression of proinflammatory genes 24 hours after reperfusion and significantly increased survival of ganglion cell layer neurons 7 days after IR injury.
CONCLUSIONS: These results suggest that an increased level of Hmgb1 and signaling via the Rage contribute to neurotoxicity after retinal IR injury.
Authors:
Galina Dvoriantchikova; Eleut Hernandez; Jeff Grant; Andrea Rachelle C Santos; Huan Yang; Dmitry Ivanov
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-09-09
Journal Detail:
Title:  Investigative ophthalmology & visual science     Volume:  52     ISSN:  1552-5783     ISO Abbreviation:  Invest. Ophthalmol. Vis. Sci.     Publication Date:  2011  
Date Detail:
Created Date:  2011-09-12     Completed Date:  2011-11-04     Revised Date:  2014-09-21    
Medline Journal Info:
Nlm Unique ID:  7703701     Medline TA:  Invest Ophthalmol Vis Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  7187-94     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Animals, Newborn
Antibodies, Neutralizing / pharmacology
Blotting, Western
Cell Survival
Cells, Cultured
Coculture Techniques
Fluorescent Antibody Technique, Indirect
HMGB1 Protein / physiology*
Intravitreal Injections
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Microscopy, Confocal
Neuroglia / pathology
Receptors, Immunologic / metabolism
Recombinant Proteins / pharmacology
Reperfusion Injury / metabolism*,  pathology
Retinal Diseases / metabolism*,  pathology
Retinal Ganglion Cells / metabolism*,  pathology
Reverse Transcriptase Polymerase Chain Reaction
Toll-Like Receptor 4 / metabolism
Grant Support
ID/Acronym/Agency:
P30 EY014801/EY/NEI NIH HHS; R21 EY020613/EY/NEI NIH HHS; R21 EY020613-02/EY/NEI NIH HHS; R21EY020613/EY/NEI NIH HHS
Chemical
Reg. No./Substance:
0/Antibodies, Neutralizing; 0/HMGB1 Protein; 0/Receptors, Immunologic; 0/Recombinant Proteins; 0/Tlr4 protein, mouse; 0/Toll-Like Receptor 4; 0/advanced glycosylation end-product receptor
Comments/Corrections

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