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Inhibition of Heat Shock Protein B8 Alleviates Retinal Dysfunction and Ganglion Cells Loss Via Autophagy Suppression in Mouse Axonal Damage

PURPOSE: Heat shock protein B8 (HspB8) can be upregulated rapidly in many pathologic processes, but its role in traumatic optic neuropathy remains unclear. In this study, we investigated the involvement of autophagy in the effects of HspB8 by using the optic nerve crush (ONC) model. METHODS: Male C5...

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Autores principales: Xie, Feijia, Li, Zongyuan, Yang, Ning, Yang, Jiayi, Hua, Dihao, Luo, Jinyuan, He, Tao, Xing, Yiqiao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Association for Research in Vision and Ophthalmology 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9248752/
https://www.ncbi.nlm.nih.gov/pubmed/35758906
http://dx.doi.org/10.1167/iovs.63.6.28
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author Xie, Feijia
Li, Zongyuan
Yang, Ning
Yang, Jiayi
Hua, Dihao
Luo, Jinyuan
He, Tao
Xing, Yiqiao
author_facet Xie, Feijia
Li, Zongyuan
Yang, Ning
Yang, Jiayi
Hua, Dihao
Luo, Jinyuan
He, Tao
Xing, Yiqiao
author_sort Xie, Feijia
collection PubMed
description PURPOSE: Heat shock protein B8 (HspB8) can be upregulated rapidly in many pathologic processes, but its role in traumatic optic neuropathy remains unclear. In this study, we investigated the involvement of autophagy in the effects of HspB8 by using the optic nerve crush (ONC) model. METHODS: Male C57BL/6J mice were intravitreally injected with recombinant adeno-associated virus type 2 (AAV2-shHspB8 or AAV2-GFP) and subsequently received ONC by a self-closing tweezers. Western blot and immunohistochemistry staining were used to evaluate the expression of HspB8. We conducted retinal flat-mount immunofluorescence to measure the quantities of retinal ganglion cells (RGCs), and full-field flash electroretinogram (ff-ERG) and optomotor response (OMR) were used to evaluate retinal function. The autophagy level was reflected by western blot, immunohistochemistry staining, and transmission electron microscope (TEM) images. We also applied 3-methyladenine (3MA) and rapamycin (Rapa) to regulate autophagy level in optic nerve injury. RESULTS: ONC stimulated the expression of HspB8. Declines of RGCs and ff-ERG b-wave amplitudes resulting from ONC can be alleviated by HspB8 downregulation. Increased autophagy activity after ONC was observed; however, this change can be reversed by intravitreal injection of AAV2-shHspB8. Furthermore, application of autophagy inhibitor 3MA had the same neuroprotective effects as AAV2-shHspB8, as illustrated by ff-ERG and quantities of RGCs. Also, protection of AAV2-shHspB8 was compromised by the autophagy activator Rapa. CONCLUSIONS: Inhibition of HspB8 in mice optic nerve injury had neuroprotective effects, which may be derived from its downregulation of autophagy.
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spelling pubmed-92487522022-07-02 Inhibition of Heat Shock Protein B8 Alleviates Retinal Dysfunction and Ganglion Cells Loss Via Autophagy Suppression in Mouse Axonal Damage Xie, Feijia Li, Zongyuan Yang, Ning Yang, Jiayi Hua, Dihao Luo, Jinyuan He, Tao Xing, Yiqiao Invest Ophthalmol Vis Sci Eye Movements, Strabismus, Amblyopia and Neuro-Ophthalmology PURPOSE: Heat shock protein B8 (HspB8) can be upregulated rapidly in many pathologic processes, but its role in traumatic optic neuropathy remains unclear. In this study, we investigated the involvement of autophagy in the effects of HspB8 by using the optic nerve crush (ONC) model. METHODS: Male C57BL/6J mice were intravitreally injected with recombinant adeno-associated virus type 2 (AAV2-shHspB8 or AAV2-GFP) and subsequently received ONC by a self-closing tweezers. Western blot and immunohistochemistry staining were used to evaluate the expression of HspB8. We conducted retinal flat-mount immunofluorescence to measure the quantities of retinal ganglion cells (RGCs), and full-field flash electroretinogram (ff-ERG) and optomotor response (OMR) were used to evaluate retinal function. The autophagy level was reflected by western blot, immunohistochemistry staining, and transmission electron microscope (TEM) images. We also applied 3-methyladenine (3MA) and rapamycin (Rapa) to regulate autophagy level in optic nerve injury. RESULTS: ONC stimulated the expression of HspB8. Declines of RGCs and ff-ERG b-wave amplitudes resulting from ONC can be alleviated by HspB8 downregulation. Increased autophagy activity after ONC was observed; however, this change can be reversed by intravitreal injection of AAV2-shHspB8. Furthermore, application of autophagy inhibitor 3MA had the same neuroprotective effects as AAV2-shHspB8, as illustrated by ff-ERG and quantities of RGCs. Also, protection of AAV2-shHspB8 was compromised by the autophagy activator Rapa. CONCLUSIONS: Inhibition of HspB8 in mice optic nerve injury had neuroprotective effects, which may be derived from its downregulation of autophagy. The Association for Research in Vision and Ophthalmology 2022-06-27 /pmc/articles/PMC9248752/ /pubmed/35758906 http://dx.doi.org/10.1167/iovs.63.6.28 Text en Copyright 2022 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
spellingShingle Eye Movements, Strabismus, Amblyopia and Neuro-Ophthalmology
Xie, Feijia
Li, Zongyuan
Yang, Ning
Yang, Jiayi
Hua, Dihao
Luo, Jinyuan
He, Tao
Xing, Yiqiao
Inhibition of Heat Shock Protein B8 Alleviates Retinal Dysfunction and Ganglion Cells Loss Via Autophagy Suppression in Mouse Axonal Damage
title Inhibition of Heat Shock Protein B8 Alleviates Retinal Dysfunction and Ganglion Cells Loss Via Autophagy Suppression in Mouse Axonal Damage
title_full Inhibition of Heat Shock Protein B8 Alleviates Retinal Dysfunction and Ganglion Cells Loss Via Autophagy Suppression in Mouse Axonal Damage
title_fullStr Inhibition of Heat Shock Protein B8 Alleviates Retinal Dysfunction and Ganglion Cells Loss Via Autophagy Suppression in Mouse Axonal Damage
title_full_unstemmed Inhibition of Heat Shock Protein B8 Alleviates Retinal Dysfunction and Ganglion Cells Loss Via Autophagy Suppression in Mouse Axonal Damage
title_short Inhibition of Heat Shock Protein B8 Alleviates Retinal Dysfunction and Ganglion Cells Loss Via Autophagy Suppression in Mouse Axonal Damage
title_sort inhibition of heat shock protein b8 alleviates retinal dysfunction and ganglion cells loss via autophagy suppression in mouse axonal damage
topic Eye Movements, Strabismus, Amblyopia and Neuro-Ophthalmology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9248752/
https://www.ncbi.nlm.nih.gov/pubmed/35758906
http://dx.doi.org/10.1167/iovs.63.6.28
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