Bcl-2转基因小鼠视神经损伤后再生轴突生长导向的研究  

Guidance of regenerative axons in optic nerve regeneration in Bcl-2 overexpressing mice

作　　者：杨柳[1] 陈东风[2] 

机构地区：[1]北京大学第一医院眼科,100034 [2]美国哈佛医学院Schepens眼科研究所

出　　处：《中华眼科杂志》2006年第2期100-103,共4页Chinese Journal of Ophthalmology

摘　　要：目的探讨视神经损伤后Bcl2高表达小鼠再生的视神经如何能长入脑内正常的靶组织。方法对生后3d(P3)的C57Bl/6J野生小鼠和Bcl2转基因小鼠进行左眼视神经夹闭损伤,立刻摘除对侧眼球,4d后处死小鼠,做视神经和脑组织切片,评估视神经的再生。视神经损伤后玻璃体内注射一种顺行性标记物———带有荧光的霍乱毒素B(CTBF),来标记视网膜神经节细胞轴突,并在视神经切片上用抗生长相关蛋白43抗体免疫荧光染色显示再生的神经轴突。结果C57Bl/6J小鼠视神经损伤后不能再生,而Bcl2转基因小鼠的视神经活跃地再生了相当长的距离,但再生的视神经轴突不能进入两侧正常的视路,而长入前脑白质。结论生后3d的Bcl2转基因小鼠一侧视神经损伤,同时摘除对侧眼球,去除正常视路的引导后,视神经轴突仍能再生,并可长入脑内,但再生的视神经轴突失去了视路中的引导,不能长入双侧中脑内的靶组织,而是在前脑形成异位神经分布。(中华眼科杂志,2006,42:100103)Objective To determine whether optic nerve can regenerate after optic nerve crush and weather the regenerating axon reaches the target in the brain in Bcl-2 overexpressing mice. Methods Left eye optic nerve crush was performed in wild-type （C57Bl/6J） and Bcl-2 transgenic mouse pups at 3 days after birth （ P3 ） , followed immediately by the opposite eyeball enucleated. Mouse pups were killed at 4 days post-surgery. Optic nerve regeneration was assessed at the sections of optic nerve and the brain. An anterograde tracer, cholera toxin B subunit conjugated with fluorescein （CTB-F） , was applied intraocularly, immediately after optic nerve crush to label retinal ganglion cell axons. Immunofluorescence staining with anti-GAP-43 was carried out to reveal regenerating axons in optic nerve sections. Results In wild-type mice, severed optic nerves failed to regenerate. In contrast, in all of the Bcl-2 transgenic mice examined, optic nerves regenerated robustly over long distances, but the regenerating fibers were found to deviat from the optic pathway and grew into the forebrain to form aberrant projection. Conclusion When the opposite eyeball is removed in P3 Bcl-2 overexpressing mice whith optic nerve was crushed in one side, the guidance from the normal optic pathway is lost, the optic nerve could regenerate and reach the brain, but the regenerating axons could not reach both side of target in the midbrain, they grow into aberrant place of forehrain.

关 键 词：基因 BCL-2 小鼠 转基因 神经再生 视神经损伤 

分 类 号：R779.1[医药卫生—眼科]