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Müller细胞重编程参与视网膜再生研究进展
赵珍珍
梁坚 [综述]
作者及单位信息
·
DOI： 10.3760/cma.j.cn115989-20200110-00019
Progress in research of Müller cell reprogramming in retinal regeneration
Zhao Zhenzhen
Liang Jian
Authors Info & Affiliations
Zhao Zhenzhen
Shanghai General Hospital, Shanghai Key Laboratory of Fundus Diseases, National Clinical Research Center for Eye Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai 200080, China
Liang Jian
Shanghai General Hospital, Shanghai Key Laboratory of Fundus Diseases, National Clinical Research Center for Eye Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai 200080, China
·
DOI： 10.3760/cma.j.cn115989-20200110-00019
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摘要

Müller细胞是视网膜主要的神经胶质细胞，对于维持视网膜稳态有重要作用。视网膜损伤后，斑马鱼Müller细胞可以通过重编程进入细胞周期增生并分化为神经元，促进视网膜完成再生修复。高等动物Müller细胞的这一能力几乎消失，导致视网膜损伤后神经元无法再生，最终造成视功能减退，甚至丢失。研究发现，虽然视网膜损伤后Müller细胞重编程过程在高等动物中不能自发激活，但可以通过诱导增强其重编程能力并实现其向神经元的转分化。这种神经元再生潜能使Müller细胞在高等动物视网膜修复再生中极有应用前景。本文围绕Müller细胞转分化为神经元的最新研究进展，从Müller细胞起源及生理病理状态、重编程机制、哺乳动物Müller细胞向神经元转分化的诱导方式、限制Müller细胞转分化为神经元的因素4个方面展开，并对Müller细胞重编程参与视网膜再生的优势与前景以及目前存在的问题进行总结。

Müller细胞;重编程;转分化;视网膜再生
ABSTRACT

Müller glia, the major type of glial cells in retina, is crucial for maintaining retinal homeostasis.Although Müller cells have the features to re-enter into the cell cycle and differentiate into neural cells for promoting retinal regeneration after retinal damage in zebrafish, these features are rigorously restricted in higher animals.It has been reported that the reprogramming of Müller cells cannot be activated spontaneously in higher animals, but the reprogramming ability and transdifferentiation to neuron can be achieved by induction.The neurogenic potential of mammalian Müller glia makes it promising in restoring retinal regeneration.In this article, we review the progresses of Müller glia-to-neuron transdifferentiation with respect of the origin, and summarize the pathophysiology characters of Müller glia, mechanisms of reprogramming, methods of inducing mammalian Müller glia to neuron and factors limiting Müller glia-to-neuron in higher animals.Besides, we propose the advantages as well as the current challenges of Müller glia-to-neuron transdifferentiation.

Müller glia;Reprogram;Transdifferentiation;Retinal regeneration
Liang Jian, Email: mocdef.labiamtoh78gnailnaij
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引用本文

赵珍珍,梁坚. Müller细胞重编程参与视网膜再生研究进展[J]. 中华实验眼科杂志,2020,38(10)：885-889.

DOI:10.3760/cma.j.cn115989-20200110-00019

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在青光眼、年龄相关性黄斑变性、视网膜色素变性等多种视网膜退行性病变中，视网膜遭受损伤后神经元发生丢失、死亡，导致视功能损伤。而在低等生物中，视网膜损伤后激活组织再生机制主要是Müller胶质细胞(Müller glia，MG)重编程分化为神经元，从而促进视网膜完成自我修复 [ 1 ]。MG是视网膜重要的神经胶质细胞，分布于视网膜内界膜到视网膜下腔的视网膜全层，参与视网膜发育并通过多种机制促进和维持视网膜稳态 [ 2 ]。在高等动物中，MG虽然在视网膜损伤后激活，但并不重编程分化为神经元，而是主要表现为反应性胶质增生，长时间的胶质增生会干扰视网膜内稳态，形成胶质瘢痕，导致神经元变性，加重视网膜退化 [ 3 ]。如何促进高等生物MG重编程和转分化并促进视网膜神经再生是当前研究热点之一。转分化是指在一定条件下，改变某种细胞的原本谱系，使之呈现出其他细胞表型的现象 [ 4 ]。研究发现，体外培养的人源MG有转分化为视杆细胞的潜能，提示MG的再生潜能在体内受到抑制 [ 5 ]。通过激发MG的这种再生潜能，有望实现疾病状态下的视网膜再生修复 [ 5 , 6 , 7 ]。本文就MG的生理活动及其重编程机制和转分化诱导方式进行综述。
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备注信息
A
梁坚，Email： mocdef.labiamtoh78gnailnaij
B
所有作者均声明不存在利益冲突
C
国家自然科学基金项目 (81700828)
国家重点研发计划项目 (2016YFC0904800、2019YFC0840607)
国家科技重大专项资助项目 (2017ZX09304010)
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