Overexpressing NeuroD1 reprograms Müller cells into various types of retinal neurons

The onset of retinal degenerative disease is often associated with neuronal loss. Therefore, how to regenerate new neurons to restore vision is an important issue. NeuroD1 is a neural transcription factor with the ability to reprogram brain astrocytes into neurons in vivo. Here, we demonstrate that...

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Bibliographic Details
Published in:Neural regeneration research 2023-05, Vol.18 (5), p.1124-1131
Main Authors: Xu, Di, Zhong, Li-Ting, Cheng, Hai-Yang, Wang, Zeng-Qiang, Chen, Xiong-Min, Feng, Ai-Ying, Chen, Wei-Yi, Chen, Gong, Xu, Ying
Format: Article
Language:English
Subjects:
amacrine cell
ganglion cell
horizontal cell
in vivo reprogramming
müller cell
neurod1
photoreceptor
regeneration
retina
retinal degeneration
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Summary:The onset of retinal degenerative disease is often associated with neuronal loss. Therefore, how to regenerate new neurons to restore vision is an important issue. NeuroD1 is a neural transcription factor with the ability to reprogram brain astrocytes into neurons in vivo. Here, we demonstrate that in adult mice, NeuroD1 can reprogram Müller cells, the principal glial cell type in the retina, to become retinal neurons. Most strikingly, ectopic expression of NeuroD1 using two different viral vectors converted Müller cells into different cell types. Specifically, AAV7m8 GFAP681::GFP-ND1 converted Müller cells into inner retinal neurons, including amacrine cells and ganglion cells. In contrast, AAV9 GFAP104::ND1-GFP converted Müller cells into outer retinal neurons such as photoreceptors and horizontal cells, with higher conversion efficiency. Furthermore, we demonstrate that Müller cell conversion induced by AAV9 GFAP104::ND1-GFP displayed clear dose- and time-dependence. These results indicate that Müller cells in adult mice are highly plastic and can be reprogrammed into various subtypes of retinal neurons.
ISSN:1673-5374
1876-7958
DOI:10.4103/1673-5374.355818