Direct optic nerve sheath (DONS) application of Schwann cells prolongs retinal ganglion cell survival in vivo

Cell-based therapies are increasingly recognized as a potential strategy to treat retinal neurodegenerative disease. Their administration, however, is normally indirect and complex, often with an inability to assess in real time their effects on cell death and their migration/integration into the ho...

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Main Authors:	Guo, L, Davis, B, Nizari, S, Normando, E M, Shi, H, Galvao, J, Turner, L, Shi, J, Clements, M, Parrinello, S, Cordeiro, M F
Format:	Online
Language:	English
Published:	Nature Publishing Group 2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4237238/

id	pubmed-4237238
recordtype	oai_dc
spelling	pubmed-42372382014-11-26 Direct optic nerve sheath (DONS) application of Schwann cells prolongs retinal ganglion cell survival in vivo Guo, L Davis, B Nizari, S Normando, E M Shi, H Galvao, J Turner, L Shi, J Clements, M Parrinello, S Cordeiro, M F Original Article Cell-based therapies are increasingly recognized as a potential strategy to treat retinal neurodegenerative disease. Their administration, however, is normally indirect and complex, often with an inability to assess in real time their effects on cell death and their migration/integration into the host retina. In the present study, using a partial optic nerve transection (pONT) rat model, we describe a new method of Schwann cell (SC) delivery (direct application to injured optic nerve sheath, SC/DONS), which was compared with intravitreal SC delivery (SC/IVT). Both SC/DONS and SC/IVT were able to be assessed in vivo using imaging to visualize retinal ganglion cell (RGC) apoptosis and SC retinal integration. RGC death in the pONT model was best fitted to the one-phase exponential decay model. Although both SC/DONS and SC/IVT altered the temporal course of RGC degeneration in pONT, SC/DONS resulted in delayed but long-lasting effects on RGC protection, compared with SC/IVT treatment. In addition, their effects on primary and secondary degeneration, and axonal regeneration, were also investigated, by histology, whole retinal counting, and modelling of RGC loss. SC/DONS was found to significantly reduce RGC apoptosis in vivo and significantly increase RGC survival by targeting secondary rather than primary degeneration. Both SC/DONS and SC/IVT were found to promote RGC axonal regrowth after optic nerve injury, with evidence of GAP-43 expression in RGC somas and axons. SC/DONS may have the potential in the treatment of optic neuropathies, such as glaucoma. We show that SC transplantation can be monitored in real time and that the protective effects of SCs are associated with targeting secondary degeneration, with implications for translating cell-based therapies to the clinic. Nature Publishing Group 2014-10 2014-10-16 /pmc/articles/PMC4237238/ /pubmed/25321467 http://dx.doi.org/10.1038/cddis.2014.399 Text en Copyright © 2014 Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ Cell Death and Disease is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution 4.0 International Licence. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons licence, users will need to obtain permission from the licence holder to reproduce the material. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Guo, L Davis, B Nizari, S Normando, E M Shi, H Galvao, J Turner, L Shi, J Clements, M Parrinello, S Cordeiro, M F
spellingShingle	Guo, L Davis, B Nizari, S Normando, E M Shi, H Galvao, J Turner, L Shi, J Clements, M Parrinello, S Cordeiro, M F Direct optic nerve sheath (DONS) application of Schwann cells prolongs retinal ganglion cell survival in vivo
author_facet	Guo, L Davis, B Nizari, S Normando, E M Shi, H Galvao, J Turner, L Shi, J Clements, M Parrinello, S Cordeiro, M F
author_sort	Guo, L
title	Direct optic nerve sheath (DONS) application of Schwann cells prolongs retinal ganglion cell survival in vivo
title_short	Direct optic nerve sheath (DONS) application of Schwann cells prolongs retinal ganglion cell survival in vivo
title_full	Direct optic nerve sheath (DONS) application of Schwann cells prolongs retinal ganglion cell survival in vivo
title_fullStr	Direct optic nerve sheath (DONS) application of Schwann cells prolongs retinal ganglion cell survival in vivo
title_full_unstemmed	Direct optic nerve sheath (DONS) application of Schwann cells prolongs retinal ganglion cell survival in vivo
title_sort	direct optic nerve sheath (dons) application of schwann cells prolongs retinal ganglion cell survival in vivo
description	Cell-based therapies are increasingly recognized as a potential strategy to treat retinal neurodegenerative disease. Their administration, however, is normally indirect and complex, often with an inability to assess in real time their effects on cell death and their migration/integration into the host retina. In the present study, using a partial optic nerve transection (pONT) rat model, we describe a new method of Schwann cell (SC) delivery (direct application to injured optic nerve sheath, SC/DONS), which was compared with intravitreal SC delivery (SC/IVT). Both SC/DONS and SC/IVT were able to be assessed in vivo using imaging to visualize retinal ganglion cell (RGC) apoptosis and SC retinal integration. RGC death in the pONT model was best fitted to the one-phase exponential decay model. Although both SC/DONS and SC/IVT altered the temporal course of RGC degeneration in pONT, SC/DONS resulted in delayed but long-lasting effects on RGC protection, compared with SC/IVT treatment. In addition, their effects on primary and secondary degeneration, and axonal regeneration, were also investigated, by histology, whole retinal counting, and modelling of RGC loss. SC/DONS was found to significantly reduce RGC apoptosis in vivo and significantly increase RGC survival by targeting secondary rather than primary degeneration. Both SC/DONS and SC/IVT were found to promote RGC axonal regrowth after optic nerve injury, with evidence of GAP-43 expression in RGC somas and axons. SC/DONS may have the potential in the treatment of optic neuropathies, such as glaucoma. We show that SC transplantation can be monitored in real time and that the protective effects of SCs are associated with targeting secondary degeneration, with implications for translating cell-based therapies to the clinic.
publisher	Nature Publishing Group
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4237238/
_version_	1613158612783333376

Direct optic nerve sheath (DONS) application of Schwann cells prolongs retinal ganglion cell survival in vivo

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