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哺乳动物视网膜中用于视力恢复的神经节细胞再生

Regeneration of Ganglion Cells for Vision Restoration in Mammalian Retinas.

作者信息

Xiao Dongchang, Jin Kangxin, Qiu Suo, Lei Qiannan, Huang Wanjing, Chen Haiqiao, Su Jing, Xu Qiang, Xu Zihui, Gou Bin, Tie Xiaoxiu, Liu Feng, Liu Sheng, Liu Yizhi, Xiang Mengqing

机构信息

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.

Guangdong Provincial Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.

出版信息

Front Cell Dev Biol. 2021 Oct 4;9:755544. doi: 10.3389/fcell.2021.755544. eCollection 2021.

Abstract

Glaucoma and other optic neuropathies affect millions of people worldwide, ultimately causing progressive and irreversible degeneration of retinal ganglion cells (RGCs) and blindness. Previous research into cell replacement therapy of these neurodegenerative diseases has been stalled due to the incapability for grafted RGCs to integrate into the retina and project properly along the long visual pathway. RGC regeneration would be a promising alternative approach but mammalian retinas lack regenerative capacity. It therefore has long been a great challenge to regenerate functional and properly projecting RGCs for vision restoration in mammals. Here we show that the transcription factors (TFs) Math5 and Brn3b together are able to reprogram mature mouse Müller glia (MG) into RGCs. The reprogrammed RGCs extend long axons that make appropriate intra-retinal and extra-retinal projections through the entire visual pathway to innervate both image-forming and non-image-forming brain targets. They exhibit typical neuronal electrophysiological properties and improve visual responses in RGC loss mouse models. Together, our data provide evidence that mammalian MG can be reprogrammed by defined TFs to achieve regeneration of functional RGCs as well as a promising new therapeutic approach to restore vision to patients with glaucoma and other optic neuropathies.

摘要

青光眼和其他视神经病变影响着全球数百万人,最终导致视网膜神经节细胞(RGCs)进行性和不可逆的退化并致盲。由于移植的RGCs无法整合到视网膜中并沿长视觉通路正常投射,此前对这些神经退行性疾病的细胞替代疗法的研究陷入停滞。RGC再生将是一种有前景的替代方法,但哺乳动物的视网膜缺乏再生能力。因此,长期以来,在哺乳动物中再生功能性且能正常投射的RGCs以恢复视力一直是一项巨大的挑战。在此,我们表明转录因子(TFs)Math5和Brn3b共同作用能够将成熟的小鼠穆勒胶质细胞(MG)重编程为RGCs。重编程后的RGCs能长出长轴突,这些轴突通过整个视觉通路进行适当的视网膜内和视网膜外投射,以支配成像和非成像的脑靶点。它们表现出典型的神经元电生理特性,并改善了RGC缺失小鼠模型中的视觉反应。总之,我们的数据证明,哺乳动物的MG可以通过特定的TFs进行重编程,以实现功能性RGCs的再生,同时也为青光眼和其他视神经病变患者恢复视力提供了一种有前景的新治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0c9/8520940/84c7a3082e84/fcell-09-755544-g001.jpg

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