ZFIN ID: ZDB-PUB-180817-3
Restoration of vision after de novo genesis of rod photoreceptors in mammalian retinas
Yao, K., Qiu, S., Wang, Y.V., Park, S.J.H., Mohns, E.J., Mehta, B., Liu, X., Chang, B., Zenisek, D., Crair, M.C., Demb, J.B., Chen, B.
Date: 2018
Source: Nature   560(7719): 484-488 (Journal)
Registered Authors: Zenisek, David
Keywords: none
MeSH Terms:
  • Animals
  • Blindness/congenital
  • Blindness/genetics
  • Blindness/therapy
  • Cell Cycle
  • Cell Proliferation/genetics
  • Cellular Reprogramming/genetics*
  • Disease Models, Animal
  • Female
  • GTP-Binding Protein alpha Subunits/genetics
  • Heterotrimeric GTP-Binding Proteins/genetics
  • Male
  • Mice
  • Neurogenesis*
  • Neuroglia/cytology
  • Neuroglia/metabolism
  • Regenerative Medicine
  • Retinal Rod Photoreceptor Cells/cytology*
  • Retinal Rod Photoreceptor Cells/metabolism*
  • Stem Cells/cytology*
  • Stem Cells/metabolism
  • Transcription Factors/genetics
  • Transcription Factors/metabolism
  • Transducin/genetics
  • Visual Cortex/cytology
  • Visual Pathways
  • beta Catenin/genetics
  • beta Catenin/metabolism
PubMed: 30111842 Full text @ Nature
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.