Maf1 regulates axonal regeneration of retinal ganglion cells after injury
Maf1 regulates axonal regeneration of retinal ganglion cells after injury
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DOI：
10.1016/j.expneurol.2021.113948
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发表时间：
2021-12-15
影响因子：
5.3
通讯作者：
Feng, Dong-Fu
中科院分区：
文献类型：
--
作者：
Chen, Di;Sun, Yi-Yu;Feng, Dong-Fu
视网膜神经节细胞（RGC）是将视觉信息从眼睛传递到大脑的唯一输出神经元。由于各种视网膜和视神经疾病，RGC胞体和轴突容易受到损伤并失去其再生能力。一个基本的问题是，操纵RGC存活的关键调节因子是否可以保护RGC免受视网膜和视神经疾病的影响。在这里，我们发现Maf 1，一个通用的转录调节因子，在RGCs从胚胎期到成年期上调。我们确定Maf 1的敲除通过改变PTEN/mTOR通路的活性促进RGCs的存活及其轴突再生，这可以被雷帕霉素阻断。我们进一步观察到Maf 1的抑制防止了视神经挤压后视网膜神经节细胞复合体变薄。这些发现揭示了敲低Maf 1对损伤后RGC存活的神经保护作用，并为创伤性视神经病变提供了潜在的治疗策略。
Retinal ganglion cells (RGCs) are the sole output neurons that carry visual information from the eye to the brain. Due to various retinal and optic nerve diseases, RGC somas and axons are vulnerable to damage and lose their regenerative capacity. A basic question is whether the manipulation of a key regulator of RGC survival can protect RGCs from retinal and optic nerve diseases. Here, we found that Maf1, a general transcriptional regulator, was upregulated in RGCs from embryonic stage to adulthood. We determined that the knockdown of Maf1 promoted the survival of RGCs and their axon regeneration through altering the activity of the PTEN/mTOR pathway, which could be blocked by rapamycin. We further observed that the inhibition of Maf1 prevented the retinal ganglion cell complex from thinning after optic nerve crush. These findings reveal a neuroprotective effect of knocking down Maf1 on RGC survival after injury and provide a potential therapeutic strategy for traumatic optic neuropathy.