Neural progenitor potential in cultured Müller glia: Effects of passaging and exogenous growth factor exposure

The Müller radial glial cell is the principal support cell of the adult mammalian retina. Recent reports suggest that these cells retain the capacity to proliferate, express phenotypes reminiscent of retinal progenitor cells (RPC) and generate neuron-like progeny. We isolated rodent Müller cells and generated cultures that could be passaged under conditions used in neural stem/progenitor cell colonies. We demonstrate that during the early period of primary culture, Müller glia proliferate into sphere colonies and express a select regimen of phenotypes normally seen in RPCs. This effect correlates temporally with the loss of retinal neurons post-dissection. When chronically maintained in vitro, Müller cells can be repeatedly passaged, and up-regulate early RPC phenotypes that are suggestive of cellular de-differentiation. Furthermore, exposure of Müller glial cultures to differentiating conditions containing growth factors stimulates Müller glia to up-regulate phenotypes associated with retinal neurons. These data provide further evidence that isolated, adult Müller glia retain functional and phenotypic features of RPCs.