通过重编程发育机制促进人视网膜神经节细胞轴突再生：mTOR 通路募集的影响。
Human retinal ganglion cell axon regeneration by recapitulating developmental mechanisms: effects of recruitment of the mTOR pathway.
机构信息
Department of Ophthalmology and Visual Science, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Department of Cell Physiology, Ruhr University of Bochum, Universitätsstraße 150, 44780 Bochum, Germany.
出版信息
Development. 2019 Jul 4;146(13):dev178012. doi: 10.1242/dev.178012.
The poor axon regeneration in the central nervous system (CNS) often leads to permanent functional deficit following disease or injury. For example, degeneration of retinal ganglion cell (RGC) axons in glaucoma leads to irreversible loss of vision. Here, we have tested the hypothesis that the mTOR pathway regulates the development of human RGCs and that its recruitment after injury facilitates axon regeneration. We observed that the mTOR pathway is active during RGC differentiation, and using the induced pluripotent stem cell model of neurogenesis show that it facilitates the differentiation, function and neuritogenesis of human RGCs. Using a microfluidic model, we demonstrate that recruitment of the mTOR pathway facilitates human RGC axon regeneration after axotomy, providing evidence that the recapitulation of developmental mechanism(s) might be a viable approach for facilitating axon regeneration in the diseased or injured human CNS, thus helping to reduce and/or recover loss of function.
中枢神经系统（CNS）中的轴突再生能力差常常导致疾病或损伤后出现永久性的功能缺陷。例如，青光眼患者的视网膜神经节细胞（RGC）轴突变性会导致不可逆转的视力丧失。在这里，我们检验了这样一个假设，即 mTOR 通路调节人 RGC 的发育，并且其在损伤后的募集有助于轴突再生。我们观察到 mTOR 通路在 RGC 分化过程中是活跃的，并且使用神经发生的诱导多能干细胞模型表明它促进了人 RGC 的分化、功能和神经突生成。我们使用微流控模型证明，mTOR 通路的募集有助于轴突切断后人类 RGC 轴突的再生，这为发育机制的再现可能是促进患病或损伤的人类中枢神经系统中轴突再生的可行方法提供了证据，从而有助于减少和/或恢复功能丧失。
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