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

Abstract 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.