AUTHOR=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. 

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

JOURNAL=Frontiers in Cellular Neuroscience

VOLUME=13

YEAR=2019

URL=https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2019.00334

DOI=10.3389/fncel.2019.00334

ISSN=1662-5102

ABSTRACT=<p>Müller glial cells (MGC) are stem cells in the retina. Although their regenerative capacity is very low in mammals, the use of MGC as stem cells to regenerate photoreceptors (PHRs) during retina degenerations, such as in retinitis pigmentosa, is being intensely studied. Changes affecting PHRs in diseased retinas have been thoroughly investigated; however, whether MGC are also affected is still unclear. We here investigated whether MGC in <italic>retinal degeneration 1</italic> (<italic>rd1</italic>) mouse, an animal model of retinitis pigmentosa, have impaired stem cell properties or structure. <italic>rd1</italic> MGC showed an altered morphology, both in culture and in the whole retina. Using mixed neuron-glial cultures obtained from newborn mice retinas, we determined that proliferation was significantly lower in <italic>rd1</italic> than in <italic>wild type (wt)</italic> MGC. Levels of stem cell markers, such as <italic>Nestin</italic> and <italic>Sox2</italic>, were also markedly reduced in <italic>rd1</italic> MGC compared to <italic>wt</italic> MGC in neuron-glial cultures and in retina cryosections, even before the onset of PHR degeneration. We then investigated whether neuron-glial crosstalk was involved in these changes. Noteworthy, <italic>Nestin</italic> expression was restored in <italic>rd1</italic> MGC in co-culture with <italic>wt</italic> neurons. Conversely, <italic>Nestin</italic> expression decreased in <italic>wt</italic> MGC in co-culture with <italic>rd1</italic> neurons, as occurred in <italic>rd1</italic> MGC in <italic>rd1</italic> neuron-glial mixed cultures. These results imply that MGC proliferation and stem cell markers are reduced in <italic>rd1</italic> retinas and might be restored by their interaction with “healthy” PHRs, suggesting that alterations in <italic>rd1</italic> PHRs lead to a disruption in neuron-glial crosstalk affecting the regenerative potential of MGC.</p>