A new calcium channel antagonist, lomerizine, alleviates secondary retinal ganglion cell death after optic nerve injury in the rat
A new calcium channel antagonist, lomerizine, alleviates secondary retinal ganglion cell death after optic nerve injury in the rat
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DOI：
10.1080/02713680500536647
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发表时间：
2006-03-01
影响因子：
2
通讯作者：
Taniguchi, T
中科院分区：
文献类型：
--
作者：
Karim, MD;Sawada, A;Taniguchi, T
目的：研究新型二苯基甲基哌嗪钙通道阻滞剂lomerizine对视神经损伤引起的大鼠轴突或视网膜损伤是否具有神经保护作用。方法：对成年Wistar白化大鼠视神经在眼球后2 mm处单侧施加局部挤压损伤。用10或30 mg/kg氯美嗪给药。每日口服2次，连用4周。在安乐死前一周，将氟金（FG）注射到双侧上丘，逆行标记存活的视网膜神经节细胞（RGCs）。视神经损伤后约1个月，对视网膜损伤进行形态学评估，并对初始病变周围视神经轴突进行组织学检查。结果：对照组RGC平均密度下降至对侧眼的65.9 +/- 1.32%，而系统应用10或30 mg/kg的lomerizine可显著提高RGC存活率，分别为88.1 +/- 0.38%和89.8 +/- 0.28%。对受损轴突的组织学检查显示，氯美嗪处理组视网膜神经节细胞的轴突密度和总数没有明显增加。我们使用的挤压力在假手术动物和实验组动物的视网膜层之间没有明显的形态学差异。结论：我们的研究结果表明，氯美嗪可能通过改善受损的轴浆血流来减轻视神经挤压损伤大鼠RGCs的继发性变性。
Purpose: We investigated whether lomerizine, a new diphenylmethylpiperazine calcium channel blocker, exerted a neuroprotective effect on axonal or retinal damage induced by optic nerve injury in the rat. Methods : A partial crush lesion was inflicted unilaterally on the optic nerve, 2 mm behind the globe, in adult Wistar albino rats. Animals were treated with the vehicle, 10 or 30 mg/kg lomerizine. Each solution was given orally twice daily for 4 weeks. One week before euthanization, Fluoro-Gold (FG) was injected into both superior colliculi to retrogradely label surviving retinal ganglion cells (RGCs). Approximately 1 month after the optic nerve injury, the retinal damage was assessed morphologically, and the optic nerve axons surrounding the initial lesion were examined histologically. Results : The mean RGC density in the control group decreased to 65.9 +/- 1.32% of the contralateral eye, whereas the systemic application of 10 or 30 mg/kg of lomerizine significantly enhanced the RGC survival to 88.1 +/- 0.38% and 89.8 +/- 0.28%, respectively. Histological examination of damaged axons revealed no significant enhancement of the density or total number of axons of the retinal ganglion cells in the lomerizine-treated group. The crush force we employed caused no significant morphological differences in the retinal layers between the sham-operated animals and the animals from the experimental groups. Conclusions : Our findings suggest that lomerizine alleviates secondary degeneration of RGCs induced by an optic nerve crush injury in the rat, presumably by improving the impaired axoplasmic flow.