Glial cells modulate retinal cell survival in rotenone-induced neural degeneration

Abstract Administration of the mitochondrial complex I inhibitor rotenone provides an excellent model to study the pathomechanism of oxidative stress-related neural degeneration diseases. In this study, we examined the glial roles in retinal cell survival and degeneration under the rotenone-induced...

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Autores principales: Hiroshi Tawarayama, Maki Inoue-Yanagimachi, Noriko Himori, Toru Nakazawa
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Lenguaje:EN
Publicado: Nature Portfolio 2021
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Acceso en línea:https://doaj.org/article/f72d7c96af7442a7bc716b68c49d4901
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spelling oai:doaj.org-article:f72d7c96af7442a7bc716b68c49d49012021-12-02T15:49:45ZGlial cells modulate retinal cell survival in rotenone-induced neural degeneration10.1038/s41598-021-90604-w2045-2322https://doaj.org/article/f72d7c96af7442a7bc716b68c49d49012021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-90604-whttps://doaj.org/toc/2045-2322Abstract Administration of the mitochondrial complex I inhibitor rotenone provides an excellent model to study the pathomechanism of oxidative stress-related neural degeneration diseases. In this study, we examined the glial roles in retinal cell survival and degeneration under the rotenone-induced oxidative stress condition. Mouse-derived Müller, microglial (BV-2), and dissociated retinal cells were used for in vitro experiments. Gene expression levels and cell viability were determined using quantitative reverse transcription-polymerase chain reaction and the alamarBlue assay, respectively. Conditioned media were prepared by stimulating glial cells with rotenone. Retinal ganglion cells (RGCs) and inner nuclear layer (INL) were visualized on rat retinal sections by immunohistochemistry and eosin/hematoxylin, respectively. Rotenone dose-dependently induced glial cell death. Treatment with rotenone or rotenone-stimulated glial cell-conditioned media altered gene expression of growth factors and inflammatory cytokines in glial cells. The viability of dissociated retinal cells significantly increased upon culturing in media conditioned with rotenone-stimulated or Müller cell-conditioned media-stimulated BV-2 cells. Furthermore, intravitreal neurotrophin-5 administration prevented the rotenone-induced reduction of RGC number and INL thickness in rats. Thus, glial cells exerted both positive and negative effects on retinal cell survival in rotenone-induced neural degeneration via altered expression of growth factors, especially upregulation of microglia-derived Ntf5, and proinflammatory cytokines.Hiroshi TawarayamaMaki Inoue-YanagimachiNoriko HimoriToru NakazawaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Hiroshi Tawarayama
Maki Inoue-Yanagimachi
Noriko Himori
Toru Nakazawa
Glial cells modulate retinal cell survival in rotenone-induced neural degeneration
description Abstract Administration of the mitochondrial complex I inhibitor rotenone provides an excellent model to study the pathomechanism of oxidative stress-related neural degeneration diseases. In this study, we examined the glial roles in retinal cell survival and degeneration under the rotenone-induced oxidative stress condition. Mouse-derived Müller, microglial (BV-2), and dissociated retinal cells were used for in vitro experiments. Gene expression levels and cell viability were determined using quantitative reverse transcription-polymerase chain reaction and the alamarBlue assay, respectively. Conditioned media were prepared by stimulating glial cells with rotenone. Retinal ganglion cells (RGCs) and inner nuclear layer (INL) were visualized on rat retinal sections by immunohistochemistry and eosin/hematoxylin, respectively. Rotenone dose-dependently induced glial cell death. Treatment with rotenone or rotenone-stimulated glial cell-conditioned media altered gene expression of growth factors and inflammatory cytokines in glial cells. The viability of dissociated retinal cells significantly increased upon culturing in media conditioned with rotenone-stimulated or Müller cell-conditioned media-stimulated BV-2 cells. Furthermore, intravitreal neurotrophin-5 administration prevented the rotenone-induced reduction of RGC number and INL thickness in rats. Thus, glial cells exerted both positive and negative effects on retinal cell survival in rotenone-induced neural degeneration via altered expression of growth factors, especially upregulation of microglia-derived Ntf5, and proinflammatory cytokines.
format article
author Hiroshi Tawarayama
Maki Inoue-Yanagimachi
Noriko Himori
Toru Nakazawa
author_facet Hiroshi Tawarayama
Maki Inoue-Yanagimachi
Noriko Himori
Toru Nakazawa
author_sort Hiroshi Tawarayama
title Glial cells modulate retinal cell survival in rotenone-induced neural degeneration
title_short Glial cells modulate retinal cell survival in rotenone-induced neural degeneration
title_full Glial cells modulate retinal cell survival in rotenone-induced neural degeneration
title_fullStr Glial cells modulate retinal cell survival in rotenone-induced neural degeneration
title_full_unstemmed Glial cells modulate retinal cell survival in rotenone-induced neural degeneration
title_sort glial cells modulate retinal cell survival in rotenone-induced neural degeneration
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/f72d7c96af7442a7bc716b68c49d4901
work_keys_str_mv AT hiroshitawarayama glialcellsmodulateretinalcellsurvivalinrotenoneinducedneuraldegeneration
AT makiinoueyanagimachi glialcellsmodulateretinalcellsurvivalinrotenoneinducedneuraldegeneration
AT norikohimori glialcellsmodulateretinalcellsurvivalinrotenoneinducedneuraldegeneration
AT torunakazawa glialcellsmodulateretinalcellsurvivalinrotenoneinducedneuraldegeneration
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