Changing the Program
Reprogramming murine Müller glia to drive photoreceptor genesis and restoration of vision
Ruth Steer |
Müller glia cells, abundant in the retina, are known to support retinal cell function. But they also have another support function: retinal regeneration. In cold-blooded vertebrates, such as zebrafish, it is well known that Müller glia can act as a source of stem cells to induce retinal repair and regeneration. But this regenerative capacity is absent in mammals; although cell proliferation might occur in response to injury, these cells do not repair or regenerate the retina. Now, a team from Icahn School of Medicine at Mount Sinai, New York, USA, have shown that they were able to reprogram Müller glia to generate rod photoreceptors, and restore light perception in a mouse model of congenital blindness (1).
Lead investigator, Bo Chen, explained: “This study opens a new pathway for potentially treating blinding diseases by manipulating our own regenerative capability to self-repair” (2). In their study, they reprogrammed Müller glia to generate rod photoreceptors through a two-step process. First, they induced Müller glia proliferation in adult mice through gene transfer of β-catenin. Second, they reprogrammed the proliferating Müller glia cells into rod photoreceptors through gene transfer of the transcription factors Otx2, Crx and Nrl. After confirming that they could generate rod photoreceptors, the team tested whether reprogramming Müller glia in a mouse model of congenital blindness (Gnat1rd17Gnatcpfl3) could restore visual function. Four weeks after Müller glial cells were reprogrammed in Gnat1rd17Gnatcpfl3 mice, the team were able to show that the mice could respond to light.
Although there is a long way to go between the laboratory bench and the clinic, Chen said that their work could “lead to extraordinary opportunities in the future where we can potentially use the same strategy to reactivate these stem cells in the diseased human eye” (2).
- K Yao et al., “Restoration of vision after de novo genesis of rod photoreceptors in mammalian retinas”, Nature, [Epub ahead of print] (2018). PMID: 30111842.
- Mount Sinai Newsroom. “Mount Sinai researchers discover how to restore vision using retinal stem cells”. Available at: bit.ly/MSinai. Accessed: August 20, 2018.