Centre for Brain Repair, University of Cambridge, Cambridge, United Kingdom.
Exp Eye Res. 2012 Nov;104:1-6. doi: 10.1016/j.exer.2012.09.002. Epub 2012 Sep 13.
Sodium channel blocking agents such as lamotrigine are potent agents for neuroprotection in several animal models of neurodegenerative and neuroinflammatory disease. We therefore explored whether lamotrigine therapy was neuroprotective in a rat model of ocular hypertension characterized by axonal injury and selective loss of retinal ganglion cells. Twenty-seven male Wistar rats were injected subcutaneously twice daily with either lamotrigine (14 mg/kg/day) or vehicle. Two weeks after the first injection, experimental ocular hypertension was induced in one eye by 532 nm trabecular laser treatment. Intraocular pressure (IOP) was monitored by rebound tonometry and four weeks after the elevation of IOP the loss of optic nerve axons was quantified relative to eyes without either IOP elevation or lamotrigine exposure. In other animals with ocular hypertension, the optic nerves were examined by immunohistochemistry for the expression of the inducible form of nitric oxide synthase (iNOS) at 7 and 28 days. Four weeks after initiation of IOP elevation, no significant difference in axonal loss was observed between rats treated with lamotrigine (30.8% ± 10.5%) or vehicle (17.8% ± 5.7%) (P = 0.19, T-test). There was no significant difference in mean IOP, peak IOP and integral IOP exposure. Furthermore, optic nerve axon counts per unit integral IOP exposure were similar in both groups (P = 0.44). The optic nerves were not positive for the expression of iNOS. In conclusion, this study provides no evidence that lamotrigine is neuroprotective for RGC axons after four weeks of experimental ocular hypertension in the rat, in a model where axonal degeneration occurs in the absence of iNOS expression.
钠通道阻断剂，如拉莫三嗪，是几种神经退行性和神经炎症性疾病的动物模型中神经保护的有效药物。因此，我们探讨了拉莫三嗪治疗是否对一种以轴突损伤和选择性视网膜神经节细胞丢失为特征的大鼠眼高压模型具有神经保护作用。27 只雄性 Wistar 大鼠每天两次皮下注射拉莫三嗪（14mg/kg/天）或载体。第一次注射后两周，通过 532nm 小梁激光治疗在一只眼诱发实验性眼高压。通过回弹眼压计监测眼内压（IOP），在 IOP 升高四周后，相对于未升高 IOP 或暴露于拉莫三嗪的眼睛，定量测量视神经轴突的丢失。在其他患有眼高压的动物中，通过免疫组织化学检测诱导型一氧化氮合酶（iNOS）的表达，在 7 天和 28 天检查视神经。在开始升高 IOP 四周后，用拉莫三嗪（30.8%±10.5%）或载体（17.8%±5.7%）治疗的大鼠之间观察到轴突丢失无显著差异（P=0.19，T 检验）。平均 IOP、峰值 IOP 和积分 IOP 暴露均无显著差异。此外，两组单位积分 IOP 暴露的视神经轴突计数相似（P=0.44）。视神经中 iNOS 的表达均为阴性。总之，这项研究没有提供证据表明拉莫三嗪在大鼠实验性眼高压四周后对 RGC 轴突具有神经保护作用，在这种模型中，轴突退化发生在没有 iNOS 表达的情况下。
