Mammalian Muller cells have been reported to possess retinal progenitor cell properties and generate new neurons after injury. This study investigates routine Muller cells under in vitro conditions for their capability of dedifferentiation into retinal progenitor cells. Muller cells were isolated from mouse retina, and proliferating cells were expanded in serum-containing medium. For dedifferentiation, the Cultured cells were transferred to serum-replacement medium (SRM) at different points in time after their isolation. Interestingly, early cell passages produced fibrous tissue in which extracellular matrix proteins and connective tissue markets were differentially expressed. In contrast, aged Muller cell cultures formed neurospheres in SRM that are characteristic for neuronal progenitor cells. These neurospheres differentiated into neuron-like cells after Cultivation on laminin/ornithine cell Culture Substrate. Here, We report for the first time that murine Muller cells can be progenitors for both, fibrous tissue cells and neuronal cells, depending on the age of the cell culture. (C) 2008 Elsevier Inc. All rights reserved.