A defective crosstalk between neurons and Müller glial cells impairs glial stem cell regenerative capacity in the rd retina

VALLESE MAURIZI, H.; VOLONTÉ, Y.A.; DIBO, M.; AYALA PEÑA, V.B.; GARELLI, A.; ZANETTI, S.R.; ROTSTEIN, N.; GERMAN, O.L.; POLITI, L.

Congreso; SAN 2018; 2018

SAN

Müller glial cells (MGCs) are stem cells in the retina. Their regenerative capacity is high in lower vertebrates, but it is very low in mammals and cannot restore photoreceptor losses during retina degeneration, such as in retinitis pigmentosa or its animal model, the rd mice. Since rd retinas show no evidence of neuronal renewal, we hypothesize that, in addition to the low regenerative capacity of MGCs and the molecular abnormalities of rd photoreceptors, the rd MGCs may have alterations affecting even more deeply their stemness potential. We here investigated whether MGCs in rd retinas present abnormalities altering their regenerative capacity. We analyzed MGC in mixed neuro-glial cultures and in slices obtained from newborn ?rd? and normal (wt) retinas. We demonstrated that rd MGCs had alterations in stem cell markers compared to wt MGCs, showing reductions in Nestin and Sox2 expression and significantly decreasing their cell cycle. They also evidenced significant morphological changes in their nuclei. We evaluated whether neuro-glial crosstalk might be responsible of these changes. Noteworthy, when we co-cultured rd MGCs with wt neurons, Nestin expression was restored in rd MGCs. Conversely, in co-cultures of wt MGCs with rd neurons, Nestin expression in MGCs decreased. These results suggest that the mutations in rd photoreceptors lead to a disruption in neuro-glial crosstalk, affecting the proliferative and regenerative capacities of rd MGCs.