Restoration of vision after de novo genesis of rod photoreceptors in mammalian retinas

Article

关键词: MULLER GLIA;    SYNAPTIC-TRANSMISSION;    CONE PHOTORECEPTORS;    NEURAL REGENERATION;    HOMEOBOX GENE;    CELL-FATE;    MICE;    TRANSDUCIN;    PROLIFERATION;    TRANSLOCATION;   

DOI  :  10.1038/s41586-018-0425-3

来源: SCIE

【 摘 要 】

In zebrafish, Muller glia (MG) are a source of retinal stem cells that can replenish damaged retinal neurons and restore vision1. In mammals, however, MG do not spontaneously re-enter the cell cycle to generate a population of stem or progenitor cells that differentiate into retinal neurons. Nevertheless, the regenerative machinery may exist in the mammalian retina, as retinal injury can stimulate MG proliferation followed by limited neurogenesis(2-7). Therefore, there is still a fundamental question regarding whether MG-derived regeneration can be exploited to restore vision in mammalian retinas. Gene transfer of beta-catenin stimulates MG proliferation in the absence of injury in mouse retinas(8). Here we report that following gene transfer of beta-catenin, cell-cycle-reactivated MG can be reprogrammed to generate rod photoreceptors by subsequent gene transfer of transcription factors essential for rod cell fate specification and determination. MG-derived rods restored visual responses in Gnat1(rd17)Gnat2(cpfl3) double mutant mice, a model of congenital blindness(9,10), throughout the visual pathway from the retina to the primary visual cortex. Together, our results provide evidence of vision restoration after de novo MG-derived genesis of rod photoreceptors in mammalian retinas.

【 授权许可】

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