Induction of Retinal Progenitors and Neurons from Mammalian Muller Glia under Defined Conditions

Background: Mammalian Muller glia are mitotic quiescent and committed. Results: Loss of p53 enhances Muller glia to proliferate and become progenitor-like cells, which differentiated to photoreceptors in vitro and incorporated into retina after transplantation. Conclusion: Progenitor potential can be induced in mammalian Muller glia. Significance: Induction of Muller glia stemness may serve as an exciting strategy for retinal repair and regeneration. Vision impairment caused by loss of retinal neurons affects millions of people worldwide, and currently, there is no effective treatment. Muller glia of mammalian retina may represent an under-recognized and potential source for regeneration of a wide range of retinal cell types, including retinal ganglion cells and photoreceptors. Here, we demonstrated that mouse Muller glia cells have the capacity to be reprogrammed into the retinal neuronal cell fate and are competent to give rise to photoreceptors under a defined culture condition. Inactivation of p53 released proliferation restriction of Muller glia and significantly enhanced the induction of retinal progenitor from Muller glia in culture. Moreover, following the ocular transplantation, the Muller glia-derived progenitors were differentiated toward the fates of photoreceptors and retinal ganglion cells. Together, these results demonstrate the feasibility of using Muller glia as a potential source for retinal repair and regeneration.