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Restoration of vision after de novo genesis of rod photoreceptors in mammalian retinas
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Restoration of vision after de novo genesis of rod photoreceptors in mammalian retinas
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Restoration of vision after de novo genesis of rod photoreceptors in mammalian retinas
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Journal Article
Restoration of vision after de novo genesis of rod photoreceptors in mammalian retinas
2018
Overview
In zebrafish, Müller glia (MG) are a source of retinal stem cells that can replenish damaged retinal neurons and restore vision
1
. 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 β-catenin stimulates MG proliferation in the absence of injury in mouse retinas
8
. 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
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.
Müller glia in mature mouse retina can be stimulated to produce rod cells; this treatment restores visual responses in a model of congenital blindness.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 14/28
/ 42
/ 42/100
/ 82/1
/ 82/51
/ 9/30
/ 9/74
/ Animals
/ Catenin
/ Cell Proliferation - genetics
/ Cellular Reprogramming - genetics
/ Female
/ Genes
/ GTP-Binding Protein alpha Subunits - genetics
/ Heterotrimeric GTP-Binding Proteins - genetics
/ Humanities and Social Sciences
/ Letter
/ Male
/ Mammals
/ Mice
/ Neurons
/ Retina
/ Retinal Rod Photoreceptor Cells - cytology
/ Retinal Rod Photoreceptor Cells - metabolism
/ Rods
/ Science
/ Transcription Factors - genetics
/ Transcription Factors - metabolism
/ Vision
