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In vivo Regeneration of Ganglion Cells for Vision Restoration in Mammalian Retinas

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 inca...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8520940/
https://www.ncbi.nlm.nih.gov/pubmed/34671605
http://dx.doi.org/10.3389/fcell.2021.755544
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author 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
author_facet 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
author_sort Xiao, Dongchang
collection PubMed
description 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. In vivo 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 in vivo regeneration of functional RGCs as well as a promising new therapeutic approach to restore vision to patients with glaucoma and other optic neuropathies.
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spelling pubmed-85209402021-10-19 In vivo Regeneration of Ganglion Cells for Vision Restoration in Mammalian Retinas 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 Front Cell Dev Biol Cell and Developmental Biology 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. In vivo 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 in vivo regeneration of functional RGCs as well as a promising new therapeutic approach to restore vision to patients with glaucoma and other optic neuropathies. Frontiers Media S.A. 2021-10-04 /pmc/articles/PMC8520940/ /pubmed/34671605 http://dx.doi.org/10.3389/fcell.2021.755544 Text en Copyright © 2021 Xiao, Jin, Qiu, Lei, Huang, Chen, Su, Xu, Xu, Gou, Tie, Liu, Liu, Liu and Xiang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
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
In vivo Regeneration of Ganglion Cells for Vision Restoration in Mammalian Retinas
title In vivo Regeneration of Ganglion Cells for Vision Restoration in Mammalian Retinas
title_full In vivo Regeneration of Ganglion Cells for Vision Restoration in Mammalian Retinas
title_fullStr In vivo Regeneration of Ganglion Cells for Vision Restoration in Mammalian Retinas
title_full_unstemmed In vivo Regeneration of Ganglion Cells for Vision Restoration in Mammalian Retinas
title_short In vivo Regeneration of Ganglion Cells for Vision Restoration in Mammalian Retinas
title_sort in vivo regeneration of ganglion cells for vision restoration in mammalian retinas
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8520940/
https://www.ncbi.nlm.nih.gov/pubmed/34671605
http://dx.doi.org/10.3389/fcell.2021.755544
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