INVESTIGADORES
SIMON Maria Victoria
artículos
Título:
Trophic Factors and Neuronal Interactions Regulate the Cell Cycle and Pax6 Expression in Müller Stem Cells
Autor/es:
M. FERNANDA INSUA; M. VICTORIA SIMÓN; ANDRÉS GARELLI; BEATRIZ DE LOS SANTOS; NORA P. ROTSTEIN; LUIS E. POLITI
Revista:
JOURNAL OF NEUROSCIENCE RESEARCH
Editorial:
WILEY-LISS, DIV JOHN WILEY & SONS INC
Referencias:
Año: 2008 vol. 86 p. 1459 - 1471
ISSN:
0360-4012
Resumen:
The finding that Mu¨ ller 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 Mu¨ ller 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 cellcycle
progression and Pax6 expression in pure Mu¨ ller
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 Mu¨ ller 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 Mu¨ ller glial cells are
regulated by molecular and cellular factors, which
might then provide potential tools for manipulating retinal
regeneration.