Cargando…

Semaphorin3A increases M1-like microglia and retinal ganglion cell apoptosis after optic nerve injury

BACKGROUND: The mechanisms leading to retinal ganglion cell (RGC) death after optic nerve injury have not been fully elucidated. Current evidence indicates that microglial activation and M1- and M2-like dynamics may be an important factor in RGC apoptosis after optic nerve crush (ONC). Semaphorin3A...

Descripción completa

Detalles Bibliográficos
Autores principales: Yun-Jia, Liu, Xi, Chen, Jie-Qiong, Zhang, Jing-Yi, Zhu, Sen, Lin, Jian, Ye
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8157735/
https://www.ncbi.nlm.nih.gov/pubmed/34039431
http://dx.doi.org/10.1186/s13578-021-00603-7
_version_ 1783699747833380864
author Yun-Jia, Liu
Xi, Chen
Jie-Qiong, Zhang
Jing-Yi, Zhu
Sen, Lin
Jian, Ye
author_facet Yun-Jia, Liu
Xi, Chen
Jie-Qiong, Zhang
Jing-Yi, Zhu
Sen, Lin
Jian, Ye
author_sort Yun-Jia, Liu
collection PubMed
description BACKGROUND: The mechanisms leading to retinal ganglion cell (RGC) death after optic nerve injury have not been fully elucidated. Current evidence indicates that microglial activation and M1- and M2-like dynamics may be an important factor in RGC apoptosis after optic nerve crush (ONC). Semaphorin3A (Sema3A) is a classic axonal guidance protein,which has been found to have a role in neuroinflammation processes. In this study, we investigated the contribution of microglial-derived Sema3A to progressive RGC apoptosis through regulating paradigm of M1- and M2-like microglia after ONC. METHOD: A mouse ONC model and a primary microglial-RGC co-culture system were used in the present study. The expression of M1- and M2-like microglial activation markers were assessed by real-time polymerase chain reaction (RT-qPCR). Histological and Western blot (WB) analyses were used to investigate the polarization patterns of microglia transitions and the levels of Sema3A. RGC apoptosis was investigated by TUNEL staining and caspase-3 detection. RESULTS: Levels of Sema3A in the mouse retina increased after ONC. Treatment of mice with the stimulating factor 1 receptor antagonist PLX3397 resulted in a decrease of retinal microglia. The levels of CD16/32 (M1) were up-regulated at days 3 and 7 post-ONC. However, CD206 (M2) declined on day 7 after ONC. Exposure to anti-Sema3A antibodies (anti-Sema3A) resulted in a decrease in the number of M1-like microglia, an increase in the number of M2-like microglia, and the amelioration of RGC apoptosis. CONCLUSIONS: An increase in microglia-derived Sema3A in the retina after ONC partially leads to a continuous increase of M1-like microglia and plays an important role in RGC apoptosis. Inhibition of Sema3A activity may be a novel approach to the prevention of RGC apoptosis after optic nerve injury. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13578-021-00603-7.
format Online
Article
Text
id pubmed-8157735
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-81577352021-05-28 Semaphorin3A increases M1-like microglia and retinal ganglion cell apoptosis after optic nerve injury Yun-Jia, Liu Xi, Chen Jie-Qiong, Zhang Jing-Yi, Zhu Sen, Lin Jian, Ye Cell Biosci Research BACKGROUND: The mechanisms leading to retinal ganglion cell (RGC) death after optic nerve injury have not been fully elucidated. Current evidence indicates that microglial activation and M1- and M2-like dynamics may be an important factor in RGC apoptosis after optic nerve crush (ONC). Semaphorin3A (Sema3A) is a classic axonal guidance protein,which has been found to have a role in neuroinflammation processes. In this study, we investigated the contribution of microglial-derived Sema3A to progressive RGC apoptosis through regulating paradigm of M1- and M2-like microglia after ONC. METHOD: A mouse ONC model and a primary microglial-RGC co-culture system were used in the present study. The expression of M1- and M2-like microglial activation markers were assessed by real-time polymerase chain reaction (RT-qPCR). Histological and Western blot (WB) analyses were used to investigate the polarization patterns of microglia transitions and the levels of Sema3A. RGC apoptosis was investigated by TUNEL staining and caspase-3 detection. RESULTS: Levels of Sema3A in the mouse retina increased after ONC. Treatment of mice with the stimulating factor 1 receptor antagonist PLX3397 resulted in a decrease of retinal microglia. The levels of CD16/32 (M1) were up-regulated at days 3 and 7 post-ONC. However, CD206 (M2) declined on day 7 after ONC. Exposure to anti-Sema3A antibodies (anti-Sema3A) resulted in a decrease in the number of M1-like microglia, an increase in the number of M2-like microglia, and the amelioration of RGC apoptosis. CONCLUSIONS: An increase in microglia-derived Sema3A in the retina after ONC partially leads to a continuous increase of M1-like microglia and plays an important role in RGC apoptosis. Inhibition of Sema3A activity may be a novel approach to the prevention of RGC apoptosis after optic nerve injury. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13578-021-00603-7. BioMed Central 2021-05-26 /pmc/articles/PMC8157735/ /pubmed/34039431 http://dx.doi.org/10.1186/s13578-021-00603-7 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Yun-Jia, Liu
Xi, Chen
Jie-Qiong, Zhang
Jing-Yi, Zhu
Sen, Lin
Jian, Ye
Semaphorin3A increases M1-like microglia and retinal ganglion cell apoptosis after optic nerve injury
title Semaphorin3A increases M1-like microglia and retinal ganglion cell apoptosis after optic nerve injury
title_full Semaphorin3A increases M1-like microglia and retinal ganglion cell apoptosis after optic nerve injury
title_fullStr Semaphorin3A increases M1-like microglia and retinal ganglion cell apoptosis after optic nerve injury
title_full_unstemmed Semaphorin3A increases M1-like microglia and retinal ganglion cell apoptosis after optic nerve injury
title_short Semaphorin3A increases M1-like microglia and retinal ganglion cell apoptosis after optic nerve injury
title_sort semaphorin3a increases m1-like microglia and retinal ganglion cell apoptosis after optic nerve injury
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8157735/
https://www.ncbi.nlm.nih.gov/pubmed/34039431
http://dx.doi.org/10.1186/s13578-021-00603-7
work_keys_str_mv AT yunjialiu semaphorin3aincreasesm1likemicrogliaandretinalganglioncellapoptosisafteropticnerveinjury
AT xichen semaphorin3aincreasesm1likemicrogliaandretinalganglioncellapoptosisafteropticnerveinjury
AT jieqiongzhang semaphorin3aincreasesm1likemicrogliaandretinalganglioncellapoptosisafteropticnerveinjury
AT jingyizhu semaphorin3aincreasesm1likemicrogliaandretinalganglioncellapoptosisafteropticnerveinjury
AT senlin semaphorin3aincreasesm1likemicrogliaandretinalganglioncellapoptosisafteropticnerveinjury
AT jianye semaphorin3aincreasesm1likemicrogliaandretinalganglioncellapoptosisafteropticnerveinjury