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Regeneration of Functional Retinal Ganglion Cells by Neuronal Identity Reprogramming

Xiaohu Wei, Zhenhao Zhang, Huan-huan Zeng, Xue-Feng Wang, Wenrong Zhan, Na Qiao, Zhen Chang, Lu Liu, Chengyu Fan, Ziwei Yang, Xiaoming Li, Yang Yang, Hongjun Liu
doi: https://doi.org/10.1101/2020.07.16.203497
Xiaohu Wei
1School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China
2Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
3College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China
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Zhenhao Zhang
1School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China
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Huan-huan Zeng
4Institute of Neuroscience, Chinese Academy of Sciences, Shanghai 200031, China
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Xue-Feng Wang
3College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China
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Wenrong Zhan
1School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China
2Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
3College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China
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Na Qiao
1School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China
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Zhen Chang
1School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China
2Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
3College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China
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Lu Liu
1School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China
2Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
3College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China
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Chengyu Fan
1School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China
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Ziwei Yang
1School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China
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Xiaoming Li
1School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China
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Yang Yang
1School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China
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Hongjun Liu
1School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China
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  • For correspondence: liuhj@shanghaitech.edu.cn
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SUMMARY

Degeneration of retinal ganglion cells (RGCs) and their axons underlies vision loss in glaucoma and various optic neuropathies. There are currently no treatments available to restore lost vision in patients affected by these diseases. Regenerating RGCs and reconnecting the retina to the brain represent an ideal therapeutic strategy; however, mammals do not have a reservoir of retinal stem/progenitor cells poised to produce new neurons in adulthood. Here, we regenerated RGCs in adult mice by direct lineage reprogramming of retinal interneurons. We successfully converted amacrine and displaced amacrine interneurons into RGCs, and observed that regenerated RGCs projected axons into brain retinorecipient areas. They convey visual information to the brain in response to visual stimulation, and are able to transmit electrical signals to postsynaptic neurons, in both normal animals and in a diseased model. The generation of functional RGCs in adult mammals points to a therapeutic strategy for vision restoration in patients.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted July 17, 2020.
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Regeneration of Functional Retinal Ganglion Cells by Neuronal Identity Reprogramming
Xiaohu Wei, Zhenhao Zhang, Huan-huan Zeng, Xue-Feng Wang, Wenrong Zhan, Na Qiao, Zhen Chang, Lu Liu, Chengyu Fan, Ziwei Yang, Xiaoming Li, Yang Yang, Hongjun Liu
bioRxiv 2020.07.16.203497; doi: https://doi.org/10.1101/2020.07.16.203497
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Regeneration of Functional Retinal Ganglion Cells by Neuronal Identity Reprogramming
Xiaohu Wei, Zhenhao Zhang, Huan-huan Zeng, Xue-Feng Wang, Wenrong Zhan, Na Qiao, Zhen Chang, Lu Liu, Chengyu Fan, Ziwei Yang, Xiaoming Li, Yang Yang, Hongjun Liu
bioRxiv 2020.07.16.203497; doi: https://doi.org/10.1101/2020.07.16.203497

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