Cargando…
Low-Intensity Pulsed Ultrasound Protects Retinal Ganglion Cell From Optic Nerve Injury Induced Apoptosis via Yes Associated Protein
Background: Low-intensity pulsed ultrasound (LIPUS) has been used in clinical studies. But little is known about its effects on the central nervous system (CNS), or its mechanism of action. Retinal ganglion cells (RGCs) are CNS neuronal cells that can be utilized as a classic model system to evaluat...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6008403/ https://www.ncbi.nlm.nih.gov/pubmed/29950973 http://dx.doi.org/10.3389/fncel.2018.00160 |
_version_ | 1783333166846574592 |
---|---|
author | Zhou, Jia-Xing Liu, Yun-Jia Chen, Xi Zhang, Xi Xu, Jie Yang, Ke Wang, Dong Lin, Sen Ye, Jian |
author_facet | Zhou, Jia-Xing Liu, Yun-Jia Chen, Xi Zhang, Xi Xu, Jie Yang, Ke Wang, Dong Lin, Sen Ye, Jian |
author_sort | Zhou, Jia-Xing |
collection | PubMed |
description | Background: Low-intensity pulsed ultrasound (LIPUS) has been used in clinical studies. But little is known about its effects on the central nervous system (CNS), or its mechanism of action. Retinal ganglion cells (RGCs) are CNS neuronal cells that can be utilized as a classic model system to evaluate outcomes of LIPUS protection from external trauma-induced retinal injury. In this study, we aim to: (1) determine the pulse energy and the capability of LIPUS in RGC viability, (2) ascertain the protective role of LIPUS in optic nerve (ON) crush-induced retinal injury, and 3) explore the cellular mechanisms of RGC apoptosis prevention by LIPUS. Methods: An ON crush model was set up to induce RGC death. LIPUS was used to treat mice eyes daily, and the retina samples were dissected for immunostaining and Western blot. The expression of yes-associated protein (YAP) and apoptosis-related proteins was detected by immunostaining and Western blot in vitro and in vivo. Apoptosis of RGCs was evaluated by TUNEL staining, the survival of RGCs and retained axons were labeled by Fluoro-gold and Tuj1 antibody, respectively. Rotenone was used to set up an in vitro cellular degenerative model and siYAP was used to interfering the expression of YAP to detect the LIPUS protective function. Results: LIPUS protected RGC from loss and apoptosis in vivo and in vitro. The ratio of cleaved/pro-caspase3 also decreased significantly under LIPUS treatment. As a cellular mechanical sensor, YAP expression increased and YAP translocated to nucleus in LIPUS stimulation group, however, phospho-YAP was found to be decreased. When YAP was inhibited, the LIPUS could not protect RGC from caspase3-dependent apoptosis. Conclusion: LIPUS prevented RGCs from apoptosis in an ON crush model and in vitro cellular degenerative model, which indicates a potential treatment for further traumatic ON injury. The mechanism of protection is dependent on YAP activation and correlated with caspase-3 signaling. |
format | Online Article Text |
id | pubmed-6008403 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-60084032018-06-27 Low-Intensity Pulsed Ultrasound Protects Retinal Ganglion Cell From Optic Nerve Injury Induced Apoptosis via Yes Associated Protein Zhou, Jia-Xing Liu, Yun-Jia Chen, Xi Zhang, Xi Xu, Jie Yang, Ke Wang, Dong Lin, Sen Ye, Jian Front Cell Neurosci Neuroscience Background: Low-intensity pulsed ultrasound (LIPUS) has been used in clinical studies. But little is known about its effects on the central nervous system (CNS), or its mechanism of action. Retinal ganglion cells (RGCs) are CNS neuronal cells that can be utilized as a classic model system to evaluate outcomes of LIPUS protection from external trauma-induced retinal injury. In this study, we aim to: (1) determine the pulse energy and the capability of LIPUS in RGC viability, (2) ascertain the protective role of LIPUS in optic nerve (ON) crush-induced retinal injury, and 3) explore the cellular mechanisms of RGC apoptosis prevention by LIPUS. Methods: An ON crush model was set up to induce RGC death. LIPUS was used to treat mice eyes daily, and the retina samples were dissected for immunostaining and Western blot. The expression of yes-associated protein (YAP) and apoptosis-related proteins was detected by immunostaining and Western blot in vitro and in vivo. Apoptosis of RGCs was evaluated by TUNEL staining, the survival of RGCs and retained axons were labeled by Fluoro-gold and Tuj1 antibody, respectively. Rotenone was used to set up an in vitro cellular degenerative model and siYAP was used to interfering the expression of YAP to detect the LIPUS protective function. Results: LIPUS protected RGC from loss and apoptosis in vivo and in vitro. The ratio of cleaved/pro-caspase3 also decreased significantly under LIPUS treatment. As a cellular mechanical sensor, YAP expression increased and YAP translocated to nucleus in LIPUS stimulation group, however, phospho-YAP was found to be decreased. When YAP was inhibited, the LIPUS could not protect RGC from caspase3-dependent apoptosis. Conclusion: LIPUS prevented RGCs from apoptosis in an ON crush model and in vitro cellular degenerative model, which indicates a potential treatment for further traumatic ON injury. The mechanism of protection is dependent on YAP activation and correlated with caspase-3 signaling. Frontiers Media S.A. 2018-06-13 /pmc/articles/PMC6008403/ /pubmed/29950973 http://dx.doi.org/10.3389/fncel.2018.00160 Text en Copyright © 2018 Zhou, Liu, Chen, Zhang, Xu, Yang, Wang, Lin and Ye. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Neuroscience Zhou, Jia-Xing Liu, Yun-Jia Chen, Xi Zhang, Xi Xu, Jie Yang, Ke Wang, Dong Lin, Sen Ye, Jian Low-Intensity Pulsed Ultrasound Protects Retinal Ganglion Cell From Optic Nerve Injury Induced Apoptosis via Yes Associated Protein |
title | Low-Intensity Pulsed Ultrasound Protects Retinal Ganglion Cell From Optic Nerve Injury Induced Apoptosis via Yes Associated Protein |
title_full | Low-Intensity Pulsed Ultrasound Protects Retinal Ganglion Cell From Optic Nerve Injury Induced Apoptosis via Yes Associated Protein |
title_fullStr | Low-Intensity Pulsed Ultrasound Protects Retinal Ganglion Cell From Optic Nerve Injury Induced Apoptosis via Yes Associated Protein |
title_full_unstemmed | Low-Intensity Pulsed Ultrasound Protects Retinal Ganglion Cell From Optic Nerve Injury Induced Apoptosis via Yes Associated Protein |
title_short | Low-Intensity Pulsed Ultrasound Protects Retinal Ganglion Cell From Optic Nerve Injury Induced Apoptosis via Yes Associated Protein |
title_sort | low-intensity pulsed ultrasound protects retinal ganglion cell from optic nerve injury induced apoptosis via yes associated protein |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6008403/ https://www.ncbi.nlm.nih.gov/pubmed/29950973 http://dx.doi.org/10.3389/fncel.2018.00160 |
work_keys_str_mv | AT zhoujiaxing lowintensitypulsedultrasoundprotectsretinalganglioncellfromopticnerveinjuryinducedapoptosisviayesassociatedprotein AT liuyunjia lowintensitypulsedultrasoundprotectsretinalganglioncellfromopticnerveinjuryinducedapoptosisviayesassociatedprotein AT chenxi lowintensitypulsedultrasoundprotectsretinalganglioncellfromopticnerveinjuryinducedapoptosisviayesassociatedprotein AT zhangxi lowintensitypulsedultrasoundprotectsretinalganglioncellfromopticnerveinjuryinducedapoptosisviayesassociatedprotein AT xujie lowintensitypulsedultrasoundprotectsretinalganglioncellfromopticnerveinjuryinducedapoptosisviayesassociatedprotein AT yangke lowintensitypulsedultrasoundprotectsretinalganglioncellfromopticnerveinjuryinducedapoptosisviayesassociatedprotein AT wangdong lowintensitypulsedultrasoundprotectsretinalganglioncellfromopticnerveinjuryinducedapoptosisviayesassociatedprotein AT linsen lowintensitypulsedultrasoundprotectsretinalganglioncellfromopticnerveinjuryinducedapoptosisviayesassociatedprotein AT yejian lowintensitypulsedultrasoundprotectsretinalganglioncellfromopticnerveinjuryinducedapoptosisviayesassociatedprotein |