Document Detail

Influence of interleukin-1 beta induction and mitogen-activated protein kinase phosphorylation on optic nerve ligation-induced matrix metalloproteinase-9 activation in the retina.
MedLine Citation:
PMID:  15037119     Owner:  NLM     Status:  MEDLINE    
Ischemic damage to the retina is a multifaceted process that results in irreversible loss of ganglion cells and blinding disease. Although the mechanisms underlying ischemia-induced ganglion cell death in the retina are not clearly understood, we have recently reported that retinal damage induced by ligation of the optic nerve results in increased matrix metalloproteinase-9 (MMP-9) synthesis and promotes ganglion cell loss. In this study, we have investigated the roles of IL-1beta and mitogen activated protein kinases in MMP-9 induction in the retina. Optic nerve ligation led to a transient increase in IL-1beta and MMP-9 levels and phosphorylation of p42/p44 mitogen activated protein kinases (extracellular signal-regulated kinases, ERK1 and ERK2) in the retina. We found no significant increase in phosphorylation of p38 MAP kinase or c-jun N-terminal kinases indicating that ERK1/2 plays a major role in MMP-9 induction. Intravitreal injection of IL-1 receptor antagonist (IL-1Ra) or MAP kinase inhibitor U0126 significantly decreased both ERK1/2 phosphorylation and MMP-9 induction suggesting that interruption of this cascade might attenuate retinal damage. In support of this, intravitreal injection of IL-1Ra and U0126 offered significant protection against optic nerve-induced retinal damage. These results suggest that optic nerve ligation-induced IL-1beta promotes retinal damage by increasing MMP-9 synthesis in the retina.
Xu Zhang; Shravan K Chintala
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Experimental eye research     Volume:  78     ISSN:  0014-4835     ISO Abbreviation:  Exp. Eye Res.     Publication Date:  2004 Apr 
Date Detail:
Created Date:  2004-03-23     Completed Date:  2004-05-25     Revised Date:  2011-08-01    
Medline Journal Info:
Nlm Unique ID:  0370707     Medline TA:  Exp Eye Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  849-60     Citation Subset:  IM    
Eye Research Institute, Oakland University, 409 Dodge Hall, Rochester, MI 48309, USA.
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MeSH Terms
Blotting, Western / methods
Butadienes / pharmacology
Enzyme Activation
Enzyme Inhibitors / pharmacology
Interleukin-1 / immunology*
Matrix Metalloproteinase 9 / metabolism*
Mice, Inbred Strains
Mitogen-Activated Protein Kinases / antagonists & inhibitors,  metabolism*
Nitriles / pharmacology
Optic Neuropathy, Ischemic / enzymology*
Receptors, Interleukin-1 / metabolism
Retina / enzymology*
Grant Support
Reg. No./Substance:
0/Butadienes; 0/Enzyme Inhibitors; 0/Interleukin-1; 0/Nitriles; 0/Receptors, Interleukin-1; 0/U 0126; EC Protein Kinases; EC Metalloproteinase 9

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