Riluzole improves functional recovery after ischemia in the rat retina

PURPOSE. Retinal ischemia leads to neuronal death. The effects of riluzole, a drug that protects against the deleterious effect of cerebral ischemia b y acting on several types of ion channels and blocking glutamatergic neurot ransmission, were investigated in a rat model of retinal ischemic injury. METHODS. Retinal ischemia was induced by increasing intraocular pressure ab ove systolic blood pressure for 30 minutes. Electroretinograms were recorde d before ischemia and at different periods of reperfusion. Riluzole was inj ected or topically applied to the eye before or after ischemia and twice da ily during the reperfusion period. Retinas were harvested for histopatholog y (toluidine blue and silver-impregnation stainings, Tdt-dUTP terminal nick -end labeling [TUNEL] method) and immunohistochemistry for cytoskeletal gli al 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 th e electroretinogram. Systemic and topical treatments with riluzole signific antly enhanced the recovery of the reduced a- and b-waves after defined rep erfusion times. Riluzole also prevented or attenuated ischemia-induced reti nal 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 again st pressure-induced ischemia. Therefore, riluzole may be a major drug for u se in protection against retinal injury.