A Defective Crosstalk Between Neurons and Müller Glial Cells in the rd1 Retina Impairs the Regenerative Potential of Glial Stem Cells

VOLONTÉ, YANEL A.; VALLESE-MAURIZI, HARMONIE; DIBO, MARCOS J.; AYALA-PEÑA, VICTORIA B.; GARELLI, ANDRÉS; ZANETTI, SAMANTA R.; TURPAUD, AXEL; CRAFT, CHERYL MAE; ROTSTEIN, NORA P.; POLITI, LUIS E.; GERMAN, OLGA L.

Frontiers in Cellular Neuroscience

Frontiers Media SA

Año: 2019 vol. 13

Müller glial cells (MGC) are stem cells in the retina. Although their regenerative capacity is very low in mammals, using MGC asstem cells to regenerate photoreceptor (PHR) losses during retina degenerations, such as in retinitis pigmentosa, is beingintensely studied. Although changes affecting PHRs in diseased retinas have been thoroughly investigated, whether MGC are alsoaffected is still unclear. We here investigated whether MGC in retinal degeneration 1 (rd1) mice, an animal model of retinitispigmentosa, have impaired stem cell properties or structure. rd1 MGC showed an altered morphology, both in culture and in thewhole retina. Using mixed neuron-glial cultures obtained from newborn mice retinas, we determined that rd1 MGC proliferationwas significantly lower than in wild type (wt) MGC. Levels of stem cell markers, such as Nestin and Sox2, were also markedlyreduced in rd1 MGC, both in neuron-glia cultures and retina cryosections, compared to wt MGC, even before the onset of PHRdegeneration. We then investigated whether neuron-glial crosstalk was involved in these changes. Noteworthy, Nestin expressionwas restored in rd1 MGC in co-culture with wt neurons. Conversely, Nestin expression decreased in wt MGC in co-culture with rd1neurons, as occurred in rd1 MGC in rd1 neuro-glial cultures. These results imply that MGC proliferation and stem cell markers arereduced in rd1 retinas and can be restored by their interaction with ?healthy? PHRs, suggesting that alterations in rd1 PHRs leadto a disruption in neuron-glial crosstalk affecting the regenerative potential of MGC.