INVESTIGADORES
ROTSTEIN Nora Patricia
artículos
Título:
Muller glial cells induce stem cell properties in retinal progenitors in vitro and promote their further differentiation into photoreceptors
Autor/es:
SIMON, M.V.; DE GENARO P.; ABRAHAN C.E.; DE LOS SANTOS EB; ROTSTEIN NR; POLITI LE
Revista:
JOURNAL OF NEUROSCIENCE RESEARCH
Editorial:
WILEY-LISS, DIV JOHN WILEY & SONS INC
Referencias:
Año: 2012 vol. 90 p. 407 - 421
ISSN:
0360-4012
Resumen:
Using stem cells to replace lost neurons is a
promising strategy for treating retina neurodegenerative diseases. Among their
multiple functions, Müller glial cells are retina stem cells, with a robust
regenerative potential in lower vertebrates but much more restricted in
mammals. In rodents, most retina progenitors exit the cell cycle immediately
after birth, differentiate as neurons and then cannot reenter the cell cycle. We
here demonstrate that in mixed cultures with Müller glial cells, rat retina
progenitor cells expressed stem cell properties, maintained their proliferative
potential, and were able to preserve these properties and remain mitotically
active after several consecutive passages. Noteworthy, these progenitors
retained the capacity to differentiate as photoreceptors, even after successive
reseedings. Müller glial cells markedly stimulated differentiation of retina progenitors;
these cells initially expressed Crx and then developed as mature photoreceptors
that expressed characteristic markers, as opsin and peripherin. Moreover, they
were light-responsive, since they decreased their cGMP levels when exposed to
light, and they also showed high affinity glutamate uptake, a characteristic of
mature photoreceptors. Our present findings propose that, besides giving rise
to new photoreceptors, Müller glial cells might instruct a pool of
undifferentiated cells to develop and preserve stem cell characteristics, even
after successive reseedings and then stimulate their differentiation as
functional photoreceptors. This complementary mechanism might contribute to
enlarge the limited regenerative capacity of mammalian Müller cells.