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

T. P. Sharma, Y. Liu, R. J. Wordinger, I. H. Pang, A. F. Clark

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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, Po0.01) and neurite outgrowth in RGCs by 141% compared to controls (n=15, Po0.05). RGC transduction with AAV2-CAG- hNRN1 prior to ONC promoted RGC survival (450%, n=3-7, Po0.05) and significantly preserved RGC function by 70% until 28 days post crush (dpc) (n=6, Po0.05) 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, Po0.001) and growth cone marker, growth-associated protein 43 (Gap43; 36%, n=3, Po0.01) were observed 28 dpc in the retinas of the treatment group compared with the control group. Significant increase in Gap43 (100%, n=5-6, Po0.05) 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.

Original languageEnglish
Article numbere1661
JournalCell Death and Disease
Volume6
Issue number2
DOIs
StatePublished - 1 Jan 2015

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Nerve Crush
Retinal Ganglion Cells
Optic Nerve
Regeneration
Cell Survival
GAP-43 Protein
Growth Cones
Neuronal Plasticity
RNA-Binding Proteins
Central Nervous System Diseases
Neuroprotective Agents
Green Fluorescent Proteins
Neurodegenerative Diseases
Synapses
Retina
Cultured Cells
Central Nervous System

Cite this

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title = "Neuritin 1 promotes retinal ganglion cell survival and axonal regeneration following optic nerve crush",
abstract = "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, Po0.01) and neurite outgrowth in RGCs by 141{\%} compared to controls (n=15, Po0.05). RGC transduction with AAV2-CAG- hNRN1 prior to ONC promoted RGC survival (450{\%}, n=3-7, Po0.05) and significantly preserved RGC function by 70{\%} until 28 days post crush (dpc) (n=6, Po0.05) 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, Po0.001) and growth cone marker, growth-associated protein 43 (Gap43; 36{\%}, n=3, Po0.01) were observed 28 dpc in the retinas of the treatment group compared with the control group. Significant increase in Gap43 (100{\%}, n=5-6, Po0.05) 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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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.

In: Cell Death and Disease, Vol. 6, No. 2, e1661, 01.01.2015.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Neuritin 1 promotes retinal ganglion cell survival and axonal regeneration following optic nerve crush

AU - Sharma, T. P.

AU - Liu, Y.

AU - Wordinger, R. J.

AU - Pang, I. H.

AU - Clark, A. F.

PY - 2015/1/1

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AB - 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, Po0.01) and neurite outgrowth in RGCs by 141% compared to controls (n=15, Po0.05). RGC transduction with AAV2-CAG- hNRN1 prior to ONC promoted RGC survival (450%, n=3-7, Po0.05) and significantly preserved RGC function by 70% until 28 days post crush (dpc) (n=6, Po0.05) 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, Po0.001) and growth cone marker, growth-associated protein 43 (Gap43; 36%, n=3, Po0.01) were observed 28 dpc in the retinas of the treatment group compared with the control group. Significant increase in Gap43 (100%, n=5-6, Po0.05) 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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