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Regeneration of Functional Retinal Ganglion Cells by Neuronal Identity Reprogramming

By 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

Posted 17 Jul 2020
bioRxiv DOI: 10.1101/2020.07.16.203497

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.

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