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Neuritin 1 promotes retinal ganglion cell survival and axonal regeneration following optic nerve crush

Neuritin 1 (Nrn1) is an extracellular glycophosphatidylinositol-linked protein that stimulates axonal plasticity, dendritic arborization and synapse maturation in the central nervous system (CNS). The purpose of this study was to evaluate the neuroprotective and axogenic properties of Nrn1 on axotom...

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Autores principales: Sharma, T P, Liu, Y, Wordinger, R J, Pang, I-H, Clark, A F
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4669798/
https://www.ncbi.nlm.nih.gov/pubmed/25719245
http://dx.doi.org/10.1038/cddis.2015.22
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author Sharma, T P
Liu, Y
Wordinger, R J
Pang, I-H
Clark, A F
author_facet Sharma, T P
Liu, Y
Wordinger, R J
Pang, I-H
Clark, A F
author_sort Sharma, T P
collection PubMed
description Neuritin 1 (Nrn1) is an extracellular glycophosphatidylinositol-linked protein that stimulates axonal plasticity, dendritic arborization and synapse maturation in the central nervous system (CNS). The purpose of this study was to evaluate the neuroprotective and axogenic properties of Nrn1 on axotomized retinal ganglion cells (RGCs) in vitro and on the in vivo optic nerve crush (ONC) mouse model. Axotomized cultured RGCs treated with recombinant hNRN1 significantly increased survival of RGCs by 21% (n=6–7, P<0.01) and neurite outgrowth in RGCs by 141% compared to controls (n=15, P<0.05). RGC transduction with AAV2-CAG–hNRN1 prior to ONC promoted RGC survival (450%, n=3–7, P<0.05) and significantly preserved RGC function by 70% until 28 days post crush (dpc) (n=6, P<0.05) compared with the control AAV2-CAG–green fluorescent protein transduction group. Significantly elevated levels of RGC marker, RNA binding protein with multiple splicing (Rbpms; 73%, n=5–8, P<0.001) and growth cone marker, growth-associated protein 43 (Gap43; 36%, n=3, P<0.01) were observed 28 dpc in the retinas of the treatment group compared with the control group. Significant increase in Gap43 (100%, n=5–6, P<0.05) expression was observed within the optic nerves of the AAV2–hNRN1 group compared to controls. In conclusion, Nrn1 exhibited neuroprotective, regenerative effects and preserved RGC function on axotomized RGCs in vitro and after axonal injury in vivo. Nrn1 is a potential therapeutic target for CNS neurodegenerative diseases.
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spelling pubmed-46697982015-12-08 Neuritin 1 promotes retinal ganglion cell survival and axonal regeneration following optic nerve crush Sharma, T P Liu, Y Wordinger, R J Pang, I-H Clark, A F Cell Death Dis Original Article Neuritin 1 (Nrn1) is an extracellular glycophosphatidylinositol-linked protein that stimulates axonal plasticity, dendritic arborization and synapse maturation in the central nervous system (CNS). The purpose of this study was to evaluate the neuroprotective and axogenic properties of Nrn1 on axotomized retinal ganglion cells (RGCs) in vitro and on the in vivo optic nerve crush (ONC) mouse model. Axotomized cultured RGCs treated with recombinant hNRN1 significantly increased survival of RGCs by 21% (n=6–7, P<0.01) and neurite outgrowth in RGCs by 141% compared to controls (n=15, P<0.05). RGC transduction with AAV2-CAG–hNRN1 prior to ONC promoted RGC survival (450%, n=3–7, P<0.05) and significantly preserved RGC function by 70% until 28 days post crush (dpc) (n=6, P<0.05) compared with the control AAV2-CAG–green fluorescent protein transduction group. Significantly elevated levels of RGC marker, RNA binding protein with multiple splicing (Rbpms; 73%, n=5–8, P<0.001) and growth cone marker, growth-associated protein 43 (Gap43; 36%, n=3, P<0.01) were observed 28 dpc in the retinas of the treatment group compared with the control group. Significant increase in Gap43 (100%, n=5–6, P<0.05) expression was observed within the optic nerves of the AAV2–hNRN1 group compared to controls. In conclusion, Nrn1 exhibited neuroprotective, regenerative effects and preserved RGC function on axotomized RGCs in vitro and after axonal injury in vivo. Nrn1 is a potential therapeutic target for CNS neurodegenerative diseases. Nature Publishing Group 2015-02 2015-02-26 /pmc/articles/PMC4669798/ /pubmed/25719245 http://dx.doi.org/10.1038/cddis.2015.22 Text en Copyright © 2015 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
spellingShingle Original Article
Sharma, T P
Liu, Y
Wordinger, R J
Pang, I-H
Clark, A F
Neuritin 1 promotes retinal ganglion cell survival and axonal regeneration following optic nerve crush
title Neuritin 1 promotes retinal ganglion cell survival and axonal regeneration following optic nerve crush
title_full Neuritin 1 promotes retinal ganglion cell survival and axonal regeneration following optic nerve crush
title_fullStr Neuritin 1 promotes retinal ganglion cell survival and axonal regeneration following optic nerve crush
title_full_unstemmed Neuritin 1 promotes retinal ganglion cell survival and axonal regeneration following optic nerve crush
title_short Neuritin 1 promotes retinal ganglion cell survival and axonal regeneration following optic nerve crush
title_sort neuritin 1 promotes retinal ganglion cell survival and axonal regeneration following optic nerve crush
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4669798/
https://www.ncbi.nlm.nih.gov/pubmed/25719245
http://dx.doi.org/10.1038/cddis.2015.22
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