Müller glial cells induce stem cell properties in retinal progenitors in vitro and promote their further differentiation into photoreceptors

SIMON, M.V.; DE GENARO P.; ABRAHAN C.E.; DE LOS SANTOS EB; ROTSTEIN NR; POLITI LE

JOURNAL OF NEUROSCIENCE RESEARCH

WILEY-LISS, DIV JOHN WILEY & SONS INC

Lugar: New York; Año: 2011

0360-4012

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.