Müller Glial Cells Promote The Differentiation Of Retinal Progenitors As Photoreceptors And Sphingosine-1-Phosphate And Docosahexaenoic Acid Prevent Their Apoptosis

SIMON, MV; DE GENARO, P; DE LOS SANTOS, B; ROTSTEIN, NP; POLITI, LE

Rio de Janeiro

Congreso; 1st Meeting of the Institute of Glia; 2011

AbstractUsing stem cells to replace lost neurons is a promising strategy for treating retinalneurodegenerative diseases. Among their multiple functions, Müller glial cells areretina stem cells, with a robust regenerative potential in lower vertebrates, which ismuch more restricted in mammals. In rodents, most retina progenitors exit the cellcycle immediately after birth, differentiate as neurons, and then cannot reenter thecell cycle. Here we demonstrate that, in mixed cultures with Müller glial cells, ratretina progenitor cells expressed stem cell properties, maintained their proliferativepotential, and were able to preserve these properties and remain mitotically activeafter several consecutive passages. Notably, these progenitors retained thecapacity to differentiate as photoreceptors, even after successive reseedings.Müller glial cells markedly stimulated differentiation of retina progenitors; thesecells initially expressed Crx and then developed as mature photoreceptors thatexpressed characteristic markers, such as opsin and peripherin. Moreover, theywere light responsive, insofar as they decreased their cGMP levels when exposedto light, and they also showed high-affinity glutamate uptake, a characteristic ofmature photoreceptors. Our present findings indicate that, in addition to giving riseto new photoreceptors, Müller glial cells might instruct a pool of undifferentiatedcells to develop and preserve stem cell characteristics, even after successivereseedings, and then stimulate their differentiation as functional photoreceptors.This complementary mechanism might contribute to enlarge the limitedregenerative capacity of mammalian Müller cells