Effects of constitutively active K-Ras on axon regeneration after optic nerve injury
Effects of constitutively active K-Ras on axon regeneration after optic nerve injury
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DOI：
10.1016/j.neulet.2023.137124
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发表时间：
2023-02-14
影响因子：
2.5
通讯作者：
Harada，Takayuki
中科院分区：
文献类型：
--
作者：
Kiyota，Naoki;Namekata，Kazuhiko;Harada，Takayuki
视神经损伤后的视觉障碍是一个严重的问题。已经尝试增强视网膜神经节细胞（RGC）再生其轴突的内在能力，并且已经提出了PI 3 K/Akt和RAF/MEK/ERK信号激活的重要性。由于这些信号与致癌信号级联共享，在这项研究中，我们专注于K-Ras的组成型活性形式K-RasV 12，以确定该分子的过表达是否可以刺激轴突再生。我们证实K-RasV 12在体外磷酸化Akt和ERK。AAV 2-K-RasV 12的玻璃体内递送在视神经损伤后一周增加了存活的RGC的数量并促进了1.0mm的轴突再生，而没有在RGC中诱导异常增殖效应。此外，AAV 2-K-RasV 12诱导了强大的RGC轴突再生，在8周内达到距离损伤部位约2.5 mm。我们的研究结果表明，AAV 2-K-RasV 12可以为快速有效地分析轴突再生的机制提供一个良好的模型。
Visual disturbance after optic nerve injury is a serious problem. Attempts have been made to enhance the intrinsic ability of retinal ganglion cells (RGCs) to regenerate their axons, and the importance of PI3K/Akt and RAF/MEK/ERK signal activation has been suggested. Since these signals are shared with oncogenic signaling cascades, in this study, we focused on a constitutively active form of K-Ras, K-RasV12, to determine if overexpression of this molecule could stimulate axon regeneration. We confirmed that K-RasV12phosphorylated Akt and ERKin vitro. Intravitreal delivery of AAV2-K-RasV12increased the number of surviving RGCs and promoted 1.0 mm of axon regeneration one week after optic nerve injury without inducing abnormal proliferative effects in the RGCs. In addition, AAV2-K-RasV12induced robust RGC axon regeneration, reaching as far as approximately 2.5 mm from the injury site, in eight weeks. Our findings suggest that AAV2-K-RasV12could provide a good model for speedy and efficient analysis of the mechanism underlying axon regenerationin vivo.