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

VALLESE-MAURIZI H.; VOLONTÉ YA; DIBO MJ; SIMON M.V.; AYALA PEÑA VB; GARELLI A; ZANETTI SR; ROTSTEIN N.P.; GERMAN O.L.; POLITI L.E.

Ciudad de Córdoba, Córdoba

Congreso; XXXIII Reunión Anual de la SAN; 2018

SAN

A defective crosstalk between neurons and Müller glial cells impairs glial stem cell regenerative capacity in the rd retina. Vallese-Maurizi H, Volonté YA., Dibo MJ., Ayala-Peña VB., Garelli A., Zanetti S., Rotstein NP., German OL., y Politi LE.Müller glial cells (MGCs) are stem cells in the retina. Their regenerative capacity 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 have abnormalities altering their regenerative capacity. We compared the expression of several stem cell markers in mixed neuro-glial cutures and in retinas obtained from rd and normal (wt) mice: rd MGCs had reduced nestin and sox2 expression and significantly decreased their cell cycle and the number of glial cells when compared to wt MGCs. In addition, the number of neurons per glial cell in rd mixed cultures was much higher than in the wt cultures, a fact that could be due to the reduced number of MGCs in the rd cultures. One possible explanation of the impaired expression of stem cell markers in rd MGCs is that the loss of rd photoreceptors could alter the normal neuro-glial crosstalk. To investigate this possibility, we co-cultured rd or wt MGCs with either, wt or rd neurons. Noteworthy, when rd MGCs were cocultured 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.