Retinal progenitor cells could differentiate into various retinal cells that made cell-replacement therapy possible. Here, we investigated the role of cellular microenvironment on their regulation and differentiation and found that the percentage of proliferating cells and the percentage of retinal ganglion cells produced from them increased, when retinal progenitor cells were cocultured with Muller glia. Muller glia conditioned medium had the similar results. It is speculated that rather than traditional supportive roles, Muller glia may have an active regulatory role inducing retinal progenitor cells to proliferate and differentiate into ganglion cells by secreting some diffusible and membrane-associated factors. Identification of Muller glia-derived factors will be made to elucidate the molecular mechanisms of neurogenesis.