中国神经再生研究(英文版) ›› 2017, Vol. 12 ›› Issue (7): 1048-1051.doi: 10.4103/1673-5374.211178

• 综述:神经损伤修复保护与再生 • 上一篇    下一篇

SoxC转录因子在视网膜发育和再生中的作用

  

  • 收稿日期:2017-06-28 出版日期:2017-07-15 发布日期:2017-07-15

SoxC transcription factors in retinal development and regeneration

Kun-Che Chang, Jonathan Hertz   

  1. Department of Ophthalmology, School of Medicine, Stanford University, Palo Alto, CA, USA
  • Received:2017-06-28 Online:2017-07-15 Published:2017-07-15
  • Contact: Kun-Che Chang, Ph.D., kunche@stanford.edu or Jonathan Hertz, Ph.D., jhertz32@gmail.com.

摘要:

 

在发育过程中,视网膜神经节细胞(RGC)从多能性视网膜祖细胞(RPC)分化而来,但关于控制轴突生长的内在和外在的机制,我们还知之甚少。

在青光眼和其他视神经退行性疾病中,RGC在视神经恶化环境中不能存活。更遗憾的是,RGC的损失是不可逆转的,并导致视力障碍和失明。全球约有6000万青光眼患者,其是造成失明的主要原因之一。目前,治疗青光眼的唯一可改变的危险因素是降低眼压(IOP);然而,IOP降低并不总是足以应付死亡的基本进展。因此,神经保护和基于细胞的疗法是制定并最终消除青光眼和其他视神经病变损失的关键治疗目标。成人动物模型损伤和疾病的刺激发育信号通路已经证明在实现这些目标方面取得了进展;然而,许多重要问题仍然是未知的。例如,可以使用控制发育的RGC表观和轴突生长的信号传导途径来刺激干细胞,从而产生可移植供体RGC的来源以替代或保护由于疾病或损伤导致的RGC损失?文中回顾了最新研究进展:(1)SoxC转录因子作为RGC表观调控和轴突生长发育的基础,以及(2)SoxC依赖机制如何在青光眼和其他视神经病变细胞疗法中的应用。

ORCID:0000-0002-0871-5612(Kun-Che Chang)

Abstract:

Glaucoma and other optic neuropathies result in optic nerve degeneration and the loss of retinal ganglion cells (RGCs) through complex signaling pathways. Although the mechanisms that regulate RGC development remain unclear, uncovering novel developmental pathways may support new strategies to regenerate the optic nerve or replace RGCs. Here we review recent studies that provide strong evidence that the Sry-related high-mobility-group C (SoxC) subfamily of transcription factors (TFs) are necessary and sufficient for axon guidance and RGC fate specification. These findings also uncover novel SoxC-dependent mechanisms that serve as master regulators during important steps of RGC development. For example, we review work showing that SoxC TFs regulate RGC axon guidance and direction through the optic chiasm towards their appropriate targets in the brain. We also review work demonstrating that Sox11 subcellular localization is, in part, controlled through small ubiquitin-like post-translational modifier (SUMO) and suggest compensatory cross-talk between Sox4 and Sox11. Furthermore, Sox4 overexpression is shown to positively drive RGC differentiation in human induced pluripotent stem cells (hiPSCs). Finally, we discuss how these findings may contribute to the advancement of regenerative and cell-based therapies to treat glaucoma and other optic nerve neuropathies.

Key words: Sox4, Sox11, retinal ganglion cell, optic nerve, regeneration, SUMOylation, cell transplantation, stem cell