Document Detail

Nitrosative stress and corneal transplant endothelial cell death during acute graft rejection.
MedLine Citation:
PMID:  17700169     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Nitrosative stress takes place in endothelial cells (EC) during corneal acute graft rejection. The purpose of this study was to evaluate the potential role of peroxynitrite on corneal EC death. METHODS: The effect of peroxynitrite was evaluated in vivo. Fifty, 250, and 500 microM in 1.5 microL of the natural or denatured peroxynitrite in 50 microM NaOH, 50 microM NaOH alone, or balanced salt solution were injected into the anterior chamber of rat eyes (n=3/group). Corneal toxic signs after injection were assessed by slit-lamp, in vivo confocal imaging, pachymetry, and EC count. The effect of peroxynitrite was also evaluated on nitrotyrosine and leucocyte elastase inhibitor/LDNase II immunohistochemistry. Human corneas were incubated with peroxynitrite and the effect on EC viability was evaluated. A specific inducible nitric oxide synthase inhibitor (iNOS) was administered systemically in rats undergoing allogeneic corneal graft rejection and the effect on EC was evaluated by EC count. RESULTS: Rat eyes receiving as little as 50 microM peroxynitrite showed a specific dose-dependent toxicity on EC. We observed an intense nitrotyrosine staining of human and rat EC exposed to peroxynitrite associated with leucocyte elastase inhibitor nuclear translocation, a noncaspase dependent apoptosis reaction. Specific inhibition of iNOS generation prevented EC death and enhanced EC survival of the grafted corneas. However, inhibition of iNOS did not have a significant influence on the incidence of graft rejection. CONCLUSION: Nitrosative stress during acute corneal graft rejection in rat eyes induces a noncaspase dependent apoptotic death in EC. Inhibition of nitric oxide production during the corneal graft rejection has protective effects on the corneal EC survival.
Jean-Louis Bourges; Alicia Torriglia; Fatemeh Valamanesh; David Benezra; Gilles Renard; Francine F Behar-Cohen
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Transplantation     Volume:  84     ISSN:  0041-1337     ISO Abbreviation:  Transplantation     Publication Date:  2007 Aug 
Date Detail:
Created Date:  2007-08-16     Completed Date:  2007-09-26     Revised Date:  2010-05-14    
Medline Journal Info:
Nlm Unique ID:  0132144     Medline TA:  Transplantation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  415-23     Citation Subset:  IM    
INSERM, UMRS, Team 17, Physiopathology of Ocular Diseases, Therapeutic Innovations, Paris, France.
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MeSH Terms
Apoptosis / drug effects,  physiology*
Cell Survival / drug effects,  physiology
Corneal Transplantation / pathology*,  physiology
Endothelium, Corneal / cytology,  drug effects,  pathology*
Graft Rejection / pathology*,  physiopathology
Imines / pharmacology
Nitric Oxide / metabolism
Nitric Oxide Synthase Type II / antagonists & inhibitors
Peroxynitrous Acid / pharmacology,  physiology*
Rats, Inbred BN
Rats, Inbred Lew
Reg. No./Substance:
0/Imines; 0/N-((3-(aminomethyl)phenyl)methyl)ethanimidamide; 10102-43-9/Nitric Oxide; 14691-52-2/Peroxynitrous Acid; EC Oxide Synthase Type II

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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