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σ(2)R/TMEM97 in retinal ganglion cell degeneration

The sigma 2 receptor (σ(2)R) was recently identified as an endoplasmic reticulum (ER) membrane protein known as transmembrane protein 97 (TMEM97). Studies have shown that σ(2)R/TMEM97 binding compounds are neuroprotective, suggesting a role of σ(2)R/TMEM97 in neurodegenerative processes. To understa...

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Autores principales: Wang, Hua, Peng, Zhiyou, Li, Yiwen, Sahn, James J., Hodges, Timothy R., Chou, Tsung-Han, Liu, Qiong, Zhou, Xuezhi, Jiao, Shuliang, Porciatti, Vittorio, Liebl, Daniel J., Martin, Stephen F., Wen, Rong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9715665/
https://www.ncbi.nlm.nih.gov/pubmed/36456686
http://dx.doi.org/10.1038/s41598-022-24537-3
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author Wang, Hua
Peng, Zhiyou
Li, Yiwen
Sahn, James J.
Hodges, Timothy R.
Chou, Tsung-Han
Liu, Qiong
Zhou, Xuezhi
Jiao, Shuliang
Porciatti, Vittorio
Liebl, Daniel J.
Martin, Stephen F.
Wen, Rong
author_facet Wang, Hua
Peng, Zhiyou
Li, Yiwen
Sahn, James J.
Hodges, Timothy R.
Chou, Tsung-Han
Liu, Qiong
Zhou, Xuezhi
Jiao, Shuliang
Porciatti, Vittorio
Liebl, Daniel J.
Martin, Stephen F.
Wen, Rong
author_sort Wang, Hua
collection PubMed
description The sigma 2 receptor (σ(2)R) was recently identified as an endoplasmic reticulum (ER) membrane protein known as transmembrane protein 97 (TMEM97). Studies have shown that σ(2)R/TMEM97 binding compounds are neuroprotective, suggesting a role of σ(2)R/TMEM97 in neurodegenerative processes. To understand the function of σ(2)R/TMEM97 in neurodegeneration pathways, we characterized ischemia-induced retinal ganglion cell (RGC) degeneration in TMEM97(−/−) mice and found that RGCs in TMEM97(−/−) mice are resistant to degeneration. In addition, intravitreal injection of a selective σ(2)R/TMEM97 ligand DKR-1677 significantly protects RGCs from ischemia-induced degeneration in wildtype mice. Our results provide conclusive evidence that σ(2)R/TMEM97 plays a role to facilitate RGC death following ischemic injury and that inhibiting the function of σ(2)R/TMEM97 is neuroprotective. This work is a breakthrough toward elucidating the biology and function of σ(2)R/TMEM97 in RGCs and likely in other σ(2)R/TMEM97 expressing neurons. Moreover, these findings support future studies to develop new neuroprotective approaches for RGC degenerative diseases by inhibiting σ(2)R/TMEM97.
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spelling pubmed-97156652022-12-03 σ(2)R/TMEM97 in retinal ganglion cell degeneration Wang, Hua Peng, Zhiyou Li, Yiwen Sahn, James J. Hodges, Timothy R. Chou, Tsung-Han Liu, Qiong Zhou, Xuezhi Jiao, Shuliang Porciatti, Vittorio Liebl, Daniel J. Martin, Stephen F. Wen, Rong Sci Rep Article The sigma 2 receptor (σ(2)R) was recently identified as an endoplasmic reticulum (ER) membrane protein known as transmembrane protein 97 (TMEM97). Studies have shown that σ(2)R/TMEM97 binding compounds are neuroprotective, suggesting a role of σ(2)R/TMEM97 in neurodegenerative processes. To understand the function of σ(2)R/TMEM97 in neurodegeneration pathways, we characterized ischemia-induced retinal ganglion cell (RGC) degeneration in TMEM97(−/−) mice and found that RGCs in TMEM97(−/−) mice are resistant to degeneration. In addition, intravitreal injection of a selective σ(2)R/TMEM97 ligand DKR-1677 significantly protects RGCs from ischemia-induced degeneration in wildtype mice. Our results provide conclusive evidence that σ(2)R/TMEM97 plays a role to facilitate RGC death following ischemic injury and that inhibiting the function of σ(2)R/TMEM97 is neuroprotective. This work is a breakthrough toward elucidating the biology and function of σ(2)R/TMEM97 in RGCs and likely in other σ(2)R/TMEM97 expressing neurons. Moreover, these findings support future studies to develop new neuroprotective approaches for RGC degenerative diseases by inhibiting σ(2)R/TMEM97. Nature Publishing Group UK 2022-12-01 /pmc/articles/PMC9715665/ /pubmed/36456686 http://dx.doi.org/10.1038/s41598-022-24537-3 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This 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/) .
spellingShingle Article
Wang, Hua
Peng, Zhiyou
Li, Yiwen
Sahn, James J.
Hodges, Timothy R.
Chou, Tsung-Han
Liu, Qiong
Zhou, Xuezhi
Jiao, Shuliang
Porciatti, Vittorio
Liebl, Daniel J.
Martin, Stephen F.
Wen, Rong
σ(2)R/TMEM97 in retinal ganglion cell degeneration
title σ(2)R/TMEM97 in retinal ganglion cell degeneration
title_full σ(2)R/TMEM97 in retinal ganglion cell degeneration
title_fullStr σ(2)R/TMEM97 in retinal ganglion cell degeneration
title_full_unstemmed σ(2)R/TMEM97 in retinal ganglion cell degeneration
title_short σ(2)R/TMEM97 in retinal ganglion cell degeneration
title_sort σ(2)r/tmem97 in retinal ganglion cell degeneration
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9715665/
https://www.ncbi.nlm.nih.gov/pubmed/36456686
http://dx.doi.org/10.1038/s41598-022-24537-3
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