Ettaiche M, Fillacier K, Widmann C, Heurteaux C, Lazdunski M
Institut de Pharmacologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique, Valbonne, France.
Invest Ophthalmol Vis Sci. 1999 Mar;40(3):729-36.
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.
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).
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.
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.
视网膜缺血会导致神经元死亡。利鲁唑是一种通过作用于多种离子通道并阻断谷氨酸能神经传递来预防脑缺血有害影响的药物，本研究在大鼠视网膜缺血损伤模型中对其作用进行了探究。
通过将眼内压升高至收缩压以上30分钟来诱导视网膜缺血。在缺血前及再灌注的不同时间段记录视网膜电图。在缺血前或缺血后对眼睛注射或局部应用利鲁唑，并在再灌注期间每天两次给药。采集视网膜用于组织病理学检查（甲苯胺蓝和银浸染染色、TdT-dUTP末端脱氧核苷酸转移酶介导的缺口末端标记法[TUNEL]）以及针对细胞骨架胶质纤维酸性蛋白和c-Jun氨基末端激酶（磷酸化JNK）的免疫组织化学检查。
30分钟的缺血导致视网膜电图的a波和b波降低。利鲁唑的全身和局部治疗显著增强了在特定再灌注时间后降低的a波和b波的恢复。利鲁唑还预防或减轻了缺血诱导的视网膜细胞死亡（坏死和凋亡），并减少了磷酸化JNK的激活、c-Jun磷酸化以及缺血损伤诱导的细胞骨架蛋白增加。
利鲁唑在体内作为一种有效的神经保护剂，可抵抗压力诱导的缺血。因此，利鲁唑可能是用于预防视网膜损伤的主要药物。
