Document Detail

Riluzole improves functional recovery after ischemia in the rat retina.
MedLine Citation:
PMID:  10067977     Owner:  NLM     Status:  MEDLINE    
PURPOSE: Retinal ischemia leads to neuronal death. The effects of riluzole, a drug that protects against the deleterious effect of cerebral ischemia by acting on several types of ion channels and blocking glutamatergic neurotransmission, were investigated in a rat model of retinal ischemic injury. METHODS: Retinal ischemia was induced by increasing intraocular pressure above systolic blood pressure for 30 minutes. Electroretinograms were recorded before ischemia and at different periods of reperfusion. Riluzole was injected or topically applied to the eye before or after ischemia and twice daily during the reperfusion period. Retinas were harvested for histopathology (toluidine blue and silver-impregnation stainings, Tdt-dUTP terminal nick-end labeling [TUNEL] method) and immunohistochemistry for cytoskeletal glial fibrillary acid protein and c-jun NH2-terminal kinase (p-JNK). RESULTS: Ischemia for 30 minutes caused a reduction of a- and b-waves of the electroretinogram. Systemic and topical treatments with riluzole significantly enhanced the recovery of the reduced a- and b-waves after defined reperfusion times. Riluzole also prevented or attenuated ischemia-induced retinal cell death (necrosis and apoptosis) and reduced the activation of p-JNK, c-jun phosphorylation, and the increase of cytoskeletal proteins induced by ischemic injury. CONCLUSIONS: Riluzole acted in vivo as a potent neuroprotective agent against pressure-induced ischemia. Therefore, riluzole may be a major drug for use in protection against retinal injury.
M Ettaiche; K Fillacier; C Widmann; C Heurteaux; M Lazdunski
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Investigative ophthalmology & visual science     Volume:  40     ISSN:  0146-0404     ISO Abbreviation:  Invest. Ophthalmol. Vis. Sci.     Publication Date:  1999 Mar 
Date Detail:
Created Date:  1999-03-10     Completed Date:  1999-03-10     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7703701     Medline TA:  Invest Ophthalmol Vis Sci     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  729-36     Citation Subset:  IM    
Institut de Pharmacologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique, Valbonne, France.
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MeSH Terms
Administration, Topical
Glial Fibrillary Acidic Protein / metabolism
Immunoenzyme Techniques
In Situ Nick-End Labeling
Nerve Degeneration / etiology,  metabolism,  pathology,  physiopathology*
Neuroprotective Agents / administration & dosage,  pharmacology*
Proto-Oncogene Proteins c-jun / metabolism
Rats, Inbred BN
Reperfusion Injury / complications,  prevention & control*
Retina / metabolism,  pathology,  physiopathology*
Retinal Degeneration / etiology,  metabolism,  pathology,  physiopathology*
Retinal Vessels*
Riluzole / administration & dosage,  pharmacology*
Reg. No./Substance:
0/Glial Fibrillary Acidic Protein; 0/Neuroprotective Agents; 0/Proto-Oncogene Proteins c-jun; 1744-22-5/Riluzole

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