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

Kai Yao, Suo Qiu, Yanbin V. Wang, Silvia J. H. Park, Ethan J. Mohns, Bhupesh Mehta, Xinran Liu, Bo Chang, David Zenisek, Michael C. Crair, Jonathan B. Demb and Bo Chen ()
Additional contact information
Kai Yao: Icahn School of Medicine at Mount Sinai
Suo Qiu: Icahn School of Medicine at Mount Sinai
Yanbin V. Wang: Yale University School of Medicine
Silvia J. H. Park: Yale University School of Medicine
Ethan J. Mohns: Yale University School of Medicine
Bhupesh Mehta: Yale University School of Medicine
Xinran Liu: Center for Cellular and Molecular Imaging, Yale University School of Medicine
Bo Chang: The Jackson Laboratory
David Zenisek: Yale University School of Medicine
Michael C. Crair: Yale University School of Medicine
Jonathan B. Demb: Yale University School of Medicine
Bo Chen: Icahn School of Medicine at Mount Sinai

Nature, 2018, vol. 560, issue 7719, 484-488

Abstract: Abstract In zebrafish, Müller 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 neurogenesis2–7. Therefore, there is still a fundamental question regarding whether MG-derived regeneration can be exploited to restore vision in mammalian retinas. Gene transfer of β-catenin stimulates MG proliferation in the absence of injury in mouse retinas8. Here we report that following gene transfer of β-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 Gnat1rd17Gnat2cpfl3 double mutant mice, a model of congenital blindness9,10, 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.

Date: 2018
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DOI: 10.1038/s41586-018-0425-3

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