摘要
目的探讨新生小鼠Bcl2高表达是否足以使视神经损伤后再生,并探讨再生的神经轴突能否到达脑内正常的靶组织。方法对出生后3d的C57BL/6J野生小鼠和Bcl2转基因小鼠进行视神经夹闭损伤,1～4d后处死小鼠,做视神经和脑组织切片,利用神经轴突顺行性标记物—带有荧光的霍乱毒素B和GAP43免疫荧光染色检查并评估视神经的再生。结果C57BL/6J野生小鼠视神经损伤后不能再生,损伤的轴突在24h内退缩,而Bcl2转基因小鼠的视神经活跃地再生了相当长的距离,并于4d后到达脑内的靶组织,但大部分再生的神经轴突沿着对侧眼的视路到达损伤同侧的脑内的靶组织,只有很少的神经轴突到达对侧。结论在出生后3d,Bcl2高表达足以使小鼠视网膜神经节细胞损伤后再生,并且再生的神经轴突可以长距离生长至中脑的靶组织,但神经轴突沿着已存在的视路进入同侧的脑内。
Objective To determine whether overexpression of Bcl-2 is sufficient to support optic nerve regeneration in mouse in the early neonatal stage, when the brain environment remains permissive for axonal growth, and whether regenerating axons follow the guidance cues to reach the appropriate targets in the brain. Methods Optic nerve crush was performed in wild-type （C57BL/6J） and Bcl-2 transgenic mouse pups at 3 days after birth （P3）. To assess optic nerve regeneration, mouse pups were allowed to survive for 1-4 days post-surgery. An anterograde tracer - cholera toxin B subunit （CTB） and anti-GAP-43 immunofluorescence were applied to reveal regenerating axons. Results In wild-type mice, severed optic nerves failed to regenerate, and most severed axons retracted within 24 hour post-surgery. In contrast, in all of the Bcl-2 transgenic mice examined, optic nerves regenerated robustly over long distances and reached their brain targets in 4 days after optic nerve crush. However, the majority of regenerating axons, appearing to follow the existing optic tract and visual pathways, entered the visual targets that were ipsilateral to the nerve injury. Much less number of regenerating axons innervated their contralateral visual targets. Conclusion Overexpression of Bcl-2 is sufficient to support the intrinsic growth mechanisms of retinal ganglion cell axons and enables robust optic nerve regeneration over long distances in vivo if the injury is incurred at 3 days after birth. However, the regenerating axons appear to follow the existing CNS pathways and innervate uninjured brain areas. （Chin J Ophtalmol , 2005, 41：832-836 ）
出处
《中华眼科杂志》
CAS
CSCD
北大核心
2005年第9期832-836,共5页
Chinese Journal of Ophthalmology
基金
美国NIH、NEI及马萨诸塞州Lion眼科研究基金资助
