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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Cell. Neurosci. | doi: 10.3389/fncel.2019.00334

A defective crosstalk between neurons and Müller glial cells in the rd1 retina impairs the regenerative potential of glial stem cells

  • 1CONICET, Instituto de Investigaciones Bioquímicas de Bahía Blanca (INIBIBB), Argentina
  • 2Departamento de Biología, Bioquímica y Farmacia, Universidad Nacional del Sur, Argentina
  • 3Department of Ophthalmology, Department of Integrative Anatomical Sciences, Keck School of Medicine, University of Southern California, United States

Abstract
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 retinal degeneration 1 (rd1) mouse, an animal model of retinitis pigmentosa, have impaired stem cell properties or structure. rd1 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 rd1 than in wild type (wt) MGC. Levels of stem cell markers, such as Nestin and Sox2, were also markedly reduced in rd1 MGC compared to wt 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, Nestin expression was restored in rd1 MGC in co-culture with wt neurons. Conversely, Nestin expression decreased in wt MGC in co-culture with rd1 neurons, as occurred in rd1 MGC in rd1 neuron-glial mixed cultures. These results imply that MGC proliferation and stem cell markers are reduced in rd1 retinas and might be restored by their interaction with “healthy” PHRs, suggesting that alterations in rd1 PHRs lead to a disruption in neuron-glial crosstalk affecting the regenerative potential of MGC.

Keywords: Müller glial cells, Stem Cells, Retinal Degeneration, Retinal regeneration, photoreceptors

Received: 28 Jan 2019; Accepted: 08 Jul 2019.

Edited by:

Mario E. GUIDO, Center for Research in Biological Chemistry Córdoba (CIQUIBIC), Argentina

Reviewed by:

Antje Grosche, Ludwig Maximilian University of Munich, Germany
Hugo Guerrero-Cazares, Mayo Clinic, United States  

Copyright: © 2019 Volonte, Valleze-Maurizi, Dibo, Ayala-Peña, Garelli, Zanetti, Turpaud, Craft, Rotstein, POLITI and German. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
PhD. LUIS E. POLITI, Instituto de Investigaciones Bioquímicas de Bahía Blanca (INIBIBB), CONICET, Bahía Blanca, Buenos Aires, Argentina, inpoliti@criba.edu.ar
PhD. Olga L. German, Departamento de Biología, Bioquímica y Farmacia, Universidad Nacional del Sur, Bahía Blanca, Buenos Aires, Argentina, olgerman@criba.edu.ar