Cargando…

Inhibition of the leucine-rich repeat protein lingo-1 enhances RGC survival in optic nerve injury

Leucine-rich repeat and immunoglobulin-like domain-containing nogo receptor-interacting protein 1 (lingo-1) is selectively expressed on neurons and oligodendrocytes in the central nervous system and acts as a negative regulator in neural repair, implying a potential role in optic neuropathy. The aim...

Descripción completa

Detalles Bibliográficos
Autores principales: Quan, Yadan, Wu, Yali, Zhan, Zongyi, Yang, Yangfan, Chen, Xiaotao, Wu, Kaili, Yu, Minbin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6913235/
https://www.ncbi.nlm.nih.gov/pubmed/31885701
http://dx.doi.org/10.3892/etm.2019.8250
_version_ 1783479624113586176
author Quan, Yadan
Wu, Yali
Zhan, Zongyi
Yang, Yangfan
Chen, Xiaotao
Wu, Kaili
Yu, Minbin
author_facet Quan, Yadan
Wu, Yali
Zhan, Zongyi
Yang, Yangfan
Chen, Xiaotao
Wu, Kaili
Yu, Minbin
author_sort Quan, Yadan
collection PubMed
description Leucine-rich repeat and immunoglobulin-like domain-containing nogo receptor-interacting protein 1 (lingo-1) is selectively expressed on neurons and oligodendrocytes in the central nervous system and acts as a negative regulator in neural repair, implying a potential role in optic neuropathy. The aim of the present study was to determine whether adeno-associated virus serotype 2 (AAV2) vector-mediated transfer of lingo-1 short hairpin RNA could reduce nerve crush-induced axonal degeneration and enhance axonal regeneration following optic nerve (ON) injury in vivo. The expression of lingo-1 was knocked down in vivo using a green fluorescent protein (GFP)-tagged AAV2 encoding lingo-1 shRNA via intravitreal injection in adult Sprague-Dawley rats. Silencing effects of AAV2-lingo-1-shRNA were confirmed by detecting GFP labelling of RGCs, and by quantifying lingo-1 expression levels with reverse transcription-quantitative polymerase chain reaction and western blotting. Rats received an intravitreal injection of AAV2-lingo-1-shRNA or negative control shRNA. The ON crush (ONC) injury was performed 2 weeks after the intravitreal injection. RGC density, lesion volume of the injured ON and the visual electrophysiology [flash visual evoked potential (F-VEP)] at different time points post-injury were determined. Transduction with lingo-1-shRNA decreased lingo-1 expression levels and promoted RGC survival following ONC. Lingo-1-shRNA promoted ON tissue repair and functional recovery. The mechanism underlying the effect of AAV2-lingo-1-shRNA on RGCs may be the phosphorylation of protein kinase B (Akt) at Ser473 and activation of the Akt signaling pathway acting downstream of lingo-1. The results of the current study indicate that the inhibition of lingo-1 may enhance RGC survival and facilitate functional recovery following ON injury, representing a promising potential strategy for the repair of optic neuropathy.
format Online
Article
Text
id pubmed-6913235
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher D.A. Spandidos
record_format MEDLINE/PubMed
spelling pubmed-69132352019-12-29 Inhibition of the leucine-rich repeat protein lingo-1 enhances RGC survival in optic nerve injury Quan, Yadan Wu, Yali Zhan, Zongyi Yang, Yangfan Chen, Xiaotao Wu, Kaili Yu, Minbin Exp Ther Med Articles Leucine-rich repeat and immunoglobulin-like domain-containing nogo receptor-interacting protein 1 (lingo-1) is selectively expressed on neurons and oligodendrocytes in the central nervous system and acts as a negative regulator in neural repair, implying a potential role in optic neuropathy. The aim of the present study was to determine whether adeno-associated virus serotype 2 (AAV2) vector-mediated transfer of lingo-1 short hairpin RNA could reduce nerve crush-induced axonal degeneration and enhance axonal regeneration following optic nerve (ON) injury in vivo. The expression of lingo-1 was knocked down in vivo using a green fluorescent protein (GFP)-tagged AAV2 encoding lingo-1 shRNA via intravitreal injection in adult Sprague-Dawley rats. Silencing effects of AAV2-lingo-1-shRNA were confirmed by detecting GFP labelling of RGCs, and by quantifying lingo-1 expression levels with reverse transcription-quantitative polymerase chain reaction and western blotting. Rats received an intravitreal injection of AAV2-lingo-1-shRNA or negative control shRNA. The ON crush (ONC) injury was performed 2 weeks after the intravitreal injection. RGC density, lesion volume of the injured ON and the visual electrophysiology [flash visual evoked potential (F-VEP)] at different time points post-injury were determined. Transduction with lingo-1-shRNA decreased lingo-1 expression levels and promoted RGC survival following ONC. Lingo-1-shRNA promoted ON tissue repair and functional recovery. The mechanism underlying the effect of AAV2-lingo-1-shRNA on RGCs may be the phosphorylation of protein kinase B (Akt) at Ser473 and activation of the Akt signaling pathway acting downstream of lingo-1. The results of the current study indicate that the inhibition of lingo-1 may enhance RGC survival and facilitate functional recovery following ON injury, representing a promising potential strategy for the repair of optic neuropathy. D.A. Spandidos 2020-01 2019-11-27 /pmc/articles/PMC6913235/ /pubmed/31885701 http://dx.doi.org/10.3892/etm.2019.8250 Text en Copyright: © Quan et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Quan, Yadan
Wu, Yali
Zhan, Zongyi
Yang, Yangfan
Chen, Xiaotao
Wu, Kaili
Yu, Minbin
Inhibition of the leucine-rich repeat protein lingo-1 enhances RGC survival in optic nerve injury
title Inhibition of the leucine-rich repeat protein lingo-1 enhances RGC survival in optic nerve injury
title_full Inhibition of the leucine-rich repeat protein lingo-1 enhances RGC survival in optic nerve injury
title_fullStr Inhibition of the leucine-rich repeat protein lingo-1 enhances RGC survival in optic nerve injury
title_full_unstemmed Inhibition of the leucine-rich repeat protein lingo-1 enhances RGC survival in optic nerve injury
title_short Inhibition of the leucine-rich repeat protein lingo-1 enhances RGC survival in optic nerve injury
title_sort inhibition of the leucine-rich repeat protein lingo-1 enhances rgc survival in optic nerve injury
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6913235/
https://www.ncbi.nlm.nih.gov/pubmed/31885701
http://dx.doi.org/10.3892/etm.2019.8250
work_keys_str_mv AT quanyadan inhibitionoftheleucinerichrepeatproteinlingo1enhancesrgcsurvivalinopticnerveinjury
AT wuyali inhibitionoftheleucinerichrepeatproteinlingo1enhancesrgcsurvivalinopticnerveinjury
AT zhanzongyi inhibitionoftheleucinerichrepeatproteinlingo1enhancesrgcsurvivalinopticnerveinjury
AT yangyangfan inhibitionoftheleucinerichrepeatproteinlingo1enhancesrgcsurvivalinopticnerveinjury
AT chenxiaotao inhibitionoftheleucinerichrepeatproteinlingo1enhancesrgcsurvivalinopticnerveinjury
AT wukaili inhibitionoftheleucinerichrepeatproteinlingo1enhancesrgcsurvivalinopticnerveinjury
AT yuminbin inhibitionoftheleucinerichrepeatproteinlingo1enhancesrgcsurvivalinopticnerveinjury