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Trophic factors and neuronal interactions regulate the cell cycle and Pax6 expression in Muller stem cells.

Authors: Insua, MF  Simon, MV  Garelli, A  De Los Santos, B  Rotstein, NP  Politi, LE 
Citation: Insua MF, etal., J Neurosci Res. 2008 May 15;86(7):1459-71. doi: 10.1002/jnr.21606.
Pubmed: (View Article at PubMed) PMID:18189319
DOI: Full-text: DOI:10.1002/jnr.21606

The finding that Muller cells have stem cell properties in the retina has led to the hypothesis that they might be a source for replacing neurons lost in neurodegenerative diseases. However, utilization of Muller cells for regenerative purposes in the mammalian eye still requires identifying those factors that regulate their multipotentiality and proliferation. In addition, because Pax6 expression is indispensable for eye development, its regulation would be required during regeneration. In the present study we investigated the regulation of cell-cycle progression and Pax6 expression in pure Muller glial cell cultures and neuroglial cocultures from rat retinas. At early times in vitro, glial cells showed high expression of Pax6 and of nestin, a stem cell marker, and of markers of cell-cycle progression; expression of these markers decreased during development in parallel with increased glial differentiation. The addition of glial-derived neurotrophic factor, basic fibroblast growth factor, and insulin restored proliferation and also Pax6 and nestin expression in glial cells. Noteworthy, in neuroglial cocultures Muller cells retained Pax6 expression for longer periods, and, in turn, neuronal progenitors preserved their proliferative potential for several days in vitro. This suggests that neuroglial interactions mutually regulate their mitogenic capacity. In addition, in glial secondary cultures incubated with insulin, many neuroblast-like cells expressed the neuronal marker NeuN. Our results suggest that the proliferative capacity and the features of eye stem cells of Muller glial cells are regulated by molecular and cellular factors, which might then provide potential tools for manipulating retinal regeneration.


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CRRD Object Information
CRRD ID: 8552378
Created: 2014-04-22
Species: All species
Last Modified: 2014-04-22
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.