Olfactory Ensheathing Cells Inhibit Gliosis in Retinal Degeneration by Downregulation of the Müller Cell Notch Signaling Pathway

Retinal regeneration and self-repair, whether in response to injury or degenerative disease, are severely impeded by glial scar formation by Müller cells (specialized retinal macroglia). We have previously demonstrated that the activation of Müller cells and gliosis in the degenerative retina are si...

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Main Authors: Jing Xie, Shujia Huo, Yijian Li, Jiaman Dai, Haiwei Xu, Zheng Qin Yin
Format: Article
Language:English
Published: SAGE Publishing 2017-06-01
Series:Cell Transplantation
Online Access:https://doi.org/10.3727/096368917X694994
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spelling doaj-34e8e7a5d3964a21b13183ec78d2e8712020-11-25T03:33:14ZengSAGE PublishingCell Transplantation0963-68971555-38922017-06-012610.3727/096368917X694994Olfactory Ensheathing Cells Inhibit Gliosis in Retinal Degeneration by Downregulation of the Müller Cell Notch Signaling PathwayJing Xie0Shujia Huo1Yijian Li2Jiaman Dai3Haiwei Xu4Zheng Qin Yin5Key Lab of Visual Damage, Regeneration and Restoration of Chongqing, Chongqing, P.R. ChinaKey Lab of Visual Damage, Regeneration and Restoration of Chongqing, Chongqing, P.R. ChinaKey Lab of Visual Damage, Regeneration and Restoration of Chongqing, Chongqing, P.R. ChinaKey Lab of Visual Damage, Regeneration and Restoration of Chongqing, Chongqing, P.R. ChinaKey Lab of Visual Damage, Regeneration and Restoration of Chongqing, Chongqing, P.R. ChinaKey Lab of Visual Damage, Regeneration and Restoration of Chongqing, Chongqing, P.R. ChinaRetinal regeneration and self-repair, whether in response to injury or degenerative disease, are severely impeded by glial scar formation by Müller cells (specialized retinal macroglia). We have previously demonstrated that the activation of Müller cells and gliosis in the degenerative retina are significantly suppressed by the subretinal transplantation of a mixture of olfactory ensheathing cells (OECs) and olfactory nerve fibroblasts. However, the underlying molecular mechanism has remained elusive. Here we transplanted purified rat OECs into the subretinal space of pigmented Royal College of Surgeons (RCS) rats, a classic rodent model of retinal degeneration. Using behavioral testing and electroretinography, we confirmed that the grafted OECs preserved the visual function of rats for 8 weeks, relative to vehicle controls (phosphate-buffered saline). Histological evaluation of outer nuclear layer thickness and composition demonstrated that more photoreceptors and ON-bipolar cells were preserved in the retinas of OEC-treated RCS rats than in controls. The grafted OECs migrated into the outer plexiform layer, inner nuclear layer, and inner plexiform layer. They interacted directly with Müller cells in the retina of RCS rats, in three distinct patterns, and secreted matrix metalloproteinases 2 and 3. Previous studies have demonstrated that rat OECs express delta-like ligand (DLL), while Müller cells express Notch3, the receptor for DLL. Here we found that the grafted OECs significantly decreased the expression, by retinal cells, of Notch signaling pathway components (including Notch3, Notch4, DLL1, DLL4, Jagged1, Hes1, and Hes5) 2 weeks after the cell transplantation and that this effect persisted for a further 2 weeks. Based on these findings, we suggest that transplanted OECs inhibit the activation of Müller cells and the associated gliosis, at least partly through suppression of the Notch pathway.https://doi.org/10.3727/096368917X694994
collection DOAJ
language English
format Article
sources DOAJ
author Jing Xie
Shujia Huo
Yijian Li
Jiaman Dai
Haiwei Xu
Zheng Qin Yin
spellingShingle Jing Xie
Shujia Huo
Yijian Li
Jiaman Dai
Haiwei Xu
Zheng Qin Yin
Olfactory Ensheathing Cells Inhibit Gliosis in Retinal Degeneration by Downregulation of the Müller Cell Notch Signaling Pathway
Cell Transplantation
author_facet Jing Xie
Shujia Huo
Yijian Li
Jiaman Dai
Haiwei Xu
Zheng Qin Yin
author_sort Jing Xie
title Olfactory Ensheathing Cells Inhibit Gliosis in Retinal Degeneration by Downregulation of the Müller Cell Notch Signaling Pathway
title_short Olfactory Ensheathing Cells Inhibit Gliosis in Retinal Degeneration by Downregulation of the Müller Cell Notch Signaling Pathway
title_full Olfactory Ensheathing Cells Inhibit Gliosis in Retinal Degeneration by Downregulation of the Müller Cell Notch Signaling Pathway
title_fullStr Olfactory Ensheathing Cells Inhibit Gliosis in Retinal Degeneration by Downregulation of the Müller Cell Notch Signaling Pathway
title_full_unstemmed Olfactory Ensheathing Cells Inhibit Gliosis in Retinal Degeneration by Downregulation of the Müller Cell Notch Signaling Pathway
title_sort olfactory ensheathing cells inhibit gliosis in retinal degeneration by downregulation of the müller cell notch signaling pathway
publisher SAGE Publishing
series Cell Transplantation
issn 0963-6897
1555-3892
publishDate 2017-06-01
description Retinal regeneration and self-repair, whether in response to injury or degenerative disease, are severely impeded by glial scar formation by Müller cells (specialized retinal macroglia). We have previously demonstrated that the activation of Müller cells and gliosis in the degenerative retina are significantly suppressed by the subretinal transplantation of a mixture of olfactory ensheathing cells (OECs) and olfactory nerve fibroblasts. However, the underlying molecular mechanism has remained elusive. Here we transplanted purified rat OECs into the subretinal space of pigmented Royal College of Surgeons (RCS) rats, a classic rodent model of retinal degeneration. Using behavioral testing and electroretinography, we confirmed that the grafted OECs preserved the visual function of rats for 8 weeks, relative to vehicle controls (phosphate-buffered saline). Histological evaluation of outer nuclear layer thickness and composition demonstrated that more photoreceptors and ON-bipolar cells were preserved in the retinas of OEC-treated RCS rats than in controls. The grafted OECs migrated into the outer plexiform layer, inner nuclear layer, and inner plexiform layer. They interacted directly with Müller cells in the retina of RCS rats, in three distinct patterns, and secreted matrix metalloproteinases 2 and 3. Previous studies have demonstrated that rat OECs express delta-like ligand (DLL), while Müller cells express Notch3, the receptor for DLL. Here we found that the grafted OECs significantly decreased the expression, by retinal cells, of Notch signaling pathway components (including Notch3, Notch4, DLL1, DLL4, Jagged1, Hes1, and Hes5) 2 weeks after the cell transplantation and that this effect persisted for a further 2 weeks. Based on these findings, we suggest that transplanted OECs inhibit the activation of Müller cells and the associated gliosis, at least partly through suppression of the Notch pathway.
url https://doi.org/10.3727/096368917X694994
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