Effects of Adult Müller Cells and Their Conditioned Media on the Survival of Stem Cell-Derived Retinal Ganglion Cells

Retinal neurons, particularly retinal ganglion cells (RGCs), are susceptible to the degenerative damage caused by different inherited conditions and environmental insults, leading to irreversible vision loss and, ultimately, blindness. Numerous strategies are being tested in different models of dege...

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Autores: Pereiro Díez, Xandra, Miltner, Adam M., La Torre, Anna, Vecino Cordero, Elena
Tipo de documento: artigo
Data de publicação:2020
País:España
Recursos:Universidad del País Vasco
Repositório:Addi. Archivo Digital para la Docencia y la Investigación
OAI Identifier:oai:addi.ehu.eus:10810/46043
Acesso em linha:http://hdl.handle.net/10810/46043
Access Level:Acceso aberto
Palavra-chave:retinal ganglion cells
Müller glia
Stem cells
retinal organoids
neuroprotection
neuritogenesis
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spelling Effects of Adult Müller Cells and Their Conditioned Media on the Survival of Stem Cell-Derived Retinal Ganglion CellsPereiro Díez, XandraMiltner, Adam M.La Torre, AnnaVecino Cordero, Elenaretinal ganglion cellsMüller gliaStem cellsretinal organoidsneuroprotectionneuritogenesisRetinal neurons, particularly retinal ganglion cells (RGCs), are susceptible to the degenerative damage caused by different inherited conditions and environmental insults, leading to irreversible vision loss and, ultimately, blindness. Numerous strategies are being tested in different models of degeneration to restore vision and, in recent years, stem cell technologies have offered novel avenues to obtain donor cells for replacement therapies. To date, stem cell–based transplantation in the retina has been attempted as treatment for photoreceptor degeneration, but the same tools could potentially be applied to other retinal cell types, including RGCs. However, RGC-like cells are not an abundant cell type in stem cell–derived cultures and, often, these cells degenerate over time in vitro. To overcome this limitation, we have taken advantage of the neuroprotective properties of Müller glia (one of the main glial cell types in the retina) and we have examined whether Müller glia and the factors they secrete could promote RGC-like cell survival in organoid cultures. Accordingly, stem cell-derived RGC-like cells were co-cultured with adult Müller cells or Müller cell-conditioned media was added to the cultures. Remarkably, RGC-like cell survival was substantially enhanced in both culture conditions, and we also observed a significant increase in their neurite length. Interestingly, Atoh7, a transcription factor required for RGC development, was up-regulated in stem cell-derived organoids exposed to conditioned media, suggesting that Müller cells may also enhance the survival of retinal progenitors and/or postmitotic precursor cells. In conclusion, Müller cells and the factors they release promote organoid-derived RGC-like cell survival, neuritogenesis, and possibly neuronal maturation.This work was supported by National Institutes of Health Grant R01EY026942 to A.L.T., and by the National Institutes of Health T32 Vision Science Training grant 4T32EY015387 to A.M.M. We also benefit from the National Eye Institute Core Facilities grant P30 EY012576. ELKARTEK KK-2019/00086 to E.V., Research groups of the UPV/EHU (GIU 2018/50) to E.V., Movilidad de personal de investigación UPV/EHU to X.P. and Programa de perfeccionamiento de personal Investigador Doctor, Gobierno Vasco (POS_2019_1_0027) to X.P.MDPI2020202020202020info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10810/46043reponame:Addi. Archivo Digital para la Docencia y la Investigacióninstname:Universidad del País VascoIngléshttps://www.mdpi.com/2073-4409/9/8/1759info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/3.0/es/2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).oai:addi.ehu.eus:10810/460432026-06-18T09:23:17Z
dc.title.none.fl_str_mv Effects of Adult Müller Cells and Their Conditioned Media on the Survival of Stem Cell-Derived Retinal Ganglion Cells
title Effects of Adult Müller Cells and Their Conditioned Media on the Survival of Stem Cell-Derived Retinal Ganglion Cells
spellingShingle Effects of Adult Müller Cells and Their Conditioned Media on the Survival of Stem Cell-Derived Retinal Ganglion Cells
Pereiro Díez, Xandra
retinal ganglion cells
Müller glia
Stem cells
retinal organoids
neuroprotection
neuritogenesis
title_short Effects of Adult Müller Cells and Their Conditioned Media on the Survival of Stem Cell-Derived Retinal Ganglion Cells
title_full Effects of Adult Müller Cells and Their Conditioned Media on the Survival of Stem Cell-Derived Retinal Ganglion Cells
title_fullStr Effects of Adult Müller Cells and Their Conditioned Media on the Survival of Stem Cell-Derived Retinal Ganglion Cells
title_full_unstemmed Effects of Adult Müller Cells and Their Conditioned Media on the Survival of Stem Cell-Derived Retinal Ganglion Cells
title_sort Effects of Adult Müller Cells and Their Conditioned Media on the Survival of Stem Cell-Derived Retinal Ganglion Cells
dc.creator.none.fl_str_mv Pereiro Díez, Xandra
Miltner, Adam M.
La Torre, Anna
Vecino Cordero, Elena
author Pereiro Díez, Xandra
author_facet Pereiro Díez, Xandra
Miltner, Adam M.
La Torre, Anna
Vecino Cordero, Elena
author_role author
author2 Miltner, Adam M.
La Torre, Anna
Vecino Cordero, Elena
author2_role author
author
author
dc.subject.none.fl_str_mv retinal ganglion cells
Müller glia
Stem cells
retinal organoids
neuroprotection
neuritogenesis
topic retinal ganglion cells
Müller glia
Stem cells
retinal organoids
neuroprotection
neuritogenesis
description Retinal neurons, particularly retinal ganglion cells (RGCs), are susceptible to the degenerative damage caused by different inherited conditions and environmental insults, leading to irreversible vision loss and, ultimately, blindness. Numerous strategies are being tested in different models of degeneration to restore vision and, in recent years, stem cell technologies have offered novel avenues to obtain donor cells for replacement therapies. To date, stem cell–based transplantation in the retina has been attempted as treatment for photoreceptor degeneration, but the same tools could potentially be applied to other retinal cell types, including RGCs. However, RGC-like cells are not an abundant cell type in stem cell–derived cultures and, often, these cells degenerate over time in vitro. To overcome this limitation, we have taken advantage of the neuroprotective properties of Müller glia (one of the main glial cell types in the retina) and we have examined whether Müller glia and the factors they secrete could promote RGC-like cell survival in organoid cultures. Accordingly, stem cell-derived RGC-like cells were co-cultured with adult Müller cells or Müller cell-conditioned media was added to the cultures. Remarkably, RGC-like cell survival was substantially enhanced in both culture conditions, and we also observed a significant increase in their neurite length. Interestingly, Atoh7, a transcription factor required for RGC development, was up-regulated in stem cell-derived organoids exposed to conditioned media, suggesting that Müller cells may also enhance the survival of retinal progenitors and/or postmitotic precursor cells. In conclusion, Müller cells and the factors they release promote organoid-derived RGC-like cell survival, neuritogenesis, and possibly neuronal maturation.
publishDate 2020
dc.date.none.fl_str_mv 2020
2020
2020
2020
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url http://hdl.handle.net/10810/46043
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv https://www.mdpi.com/2073-4409/9/8/1759
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv openAccess
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dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Addi. Archivo Digital para la Docencia y la Investigación
instname:Universidad del País Vasco
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