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Sigma 1 Receptor Contributes to Astrocyte-Mediated Retinal Ganglion Cell Protection
PURPOSE: Sigma 1 receptor (S1R) is expressed in retinal ganglion cells (RGCs) and astrocytes, and its activation is neuroprotective. We evaluated the contribution of S1R within optic nerve head astrocytes (ONHAs) to growth and survival of RGCs in vitro. METHODS: Wild-type (WT) RGCs and WT or S1R kno...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Association for Research in Vision and Ophthalmology
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8819349/ https://www.ncbi.nlm.nih.gov/pubmed/35103752 http://dx.doi.org/10.1167/iovs.63.2.1 |
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author | Zhao, Jing Gonsalvez, Graydon B. Mysona, Barbara A. Smith, Sylvia B. Bollinger, Kathryn E. |
author_facet | Zhao, Jing Gonsalvez, Graydon B. Mysona, Barbara A. Smith, Sylvia B. Bollinger, Kathryn E. |
author_sort | Zhao, Jing |
collection | PubMed |
description | PURPOSE: Sigma 1 receptor (S1R) is expressed in retinal ganglion cells (RGCs) and astrocytes, and its activation is neuroprotective. We evaluated the contribution of S1R within optic nerve head astrocytes (ONHAs) to growth and survival of RGCs in vitro. METHODS: Wild-type (WT) RGCs and WT or S1R knockout (S1R KO) ONHAs were cocultured for 2, 4, or 7 days. Total and maximal neurite length, neurite root, and extremity counts were measured. Cell death was measured using a TUNEL assay. Signal transducer and activator of transcription 3 phosphorylation levels were evaluated in ONHA-derived lysates by immunoblotting. RESULTS: The coculture of WT RGCs with WT or S1R KO ONHAs increased the total and maximal neurite length. Neurite root and extremity counts increased at 4 and 7 days when WT RGCs were cocultured with WT or S1R KO ONHAs. At all timepoints, the total and maximal neurite length decreased for WT RGCs in coculture with S1R KO ONHAs compared with WT ONHAs. Root and extremity counts decreased for WT RGCs in coculture with S1R KO ONHAs compared with WT ONHAs at 2 and 7, but not 4 days. RGC apoptosis increased in S1R KO ONHA coculture and S1R KO-conditioned medium, compared with WT ONHA coculture or WT-conditioned medium. S1R KO ONHA-derived lysates showed decreased phosphorylated signal transducer and activator of transcription 3 levels compared with WT ONHA-derived lysates. CONCLUSIONS: The absence of S1R within ONHAs has a deleterious effect on RGC neurite growth and RGC survival, reflected in analysis of WT RGC + S1R KO ONHA indirect cocultures. The data suggest that S1R may enhance ganglion cell survival via glia-mediated mechanisms. |
format | Online Article Text |
id | pubmed-8819349 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | The Association for Research in Vision and Ophthalmology |
record_format | MEDLINE/PubMed |
spelling | pubmed-88193492022-02-18 Sigma 1 Receptor Contributes to Astrocyte-Mediated Retinal Ganglion Cell Protection Zhao, Jing Gonsalvez, Graydon B. Mysona, Barbara A. Smith, Sylvia B. Bollinger, Kathryn E. Invest Ophthalmol Vis Sci Retinal Cell Biology PURPOSE: Sigma 1 receptor (S1R) is expressed in retinal ganglion cells (RGCs) and astrocytes, and its activation is neuroprotective. We evaluated the contribution of S1R within optic nerve head astrocytes (ONHAs) to growth and survival of RGCs in vitro. METHODS: Wild-type (WT) RGCs and WT or S1R knockout (S1R KO) ONHAs were cocultured for 2, 4, or 7 days. Total and maximal neurite length, neurite root, and extremity counts were measured. Cell death was measured using a TUNEL assay. Signal transducer and activator of transcription 3 phosphorylation levels were evaluated in ONHA-derived lysates by immunoblotting. RESULTS: The coculture of WT RGCs with WT or S1R KO ONHAs increased the total and maximal neurite length. Neurite root and extremity counts increased at 4 and 7 days when WT RGCs were cocultured with WT or S1R KO ONHAs. At all timepoints, the total and maximal neurite length decreased for WT RGCs in coculture with S1R KO ONHAs compared with WT ONHAs. Root and extremity counts decreased for WT RGCs in coculture with S1R KO ONHAs compared with WT ONHAs at 2 and 7, but not 4 days. RGC apoptosis increased in S1R KO ONHA coculture and S1R KO-conditioned medium, compared with WT ONHA coculture or WT-conditioned medium. S1R KO ONHA-derived lysates showed decreased phosphorylated signal transducer and activator of transcription 3 levels compared with WT ONHA-derived lysates. CONCLUSIONS: The absence of S1R within ONHAs has a deleterious effect on RGC neurite growth and RGC survival, reflected in analysis of WT RGC + S1R KO ONHA indirect cocultures. The data suggest that S1R may enhance ganglion cell survival via glia-mediated mechanisms. The Association for Research in Vision and Ophthalmology 2022-02-01 /pmc/articles/PMC8819349/ /pubmed/35103752 http://dx.doi.org/10.1167/iovs.63.2.1 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 | Retinal Cell Biology Zhao, Jing Gonsalvez, Graydon B. Mysona, Barbara A. Smith, Sylvia B. Bollinger, Kathryn E. Sigma 1 Receptor Contributes to Astrocyte-Mediated Retinal Ganglion Cell Protection |
title | Sigma 1 Receptor Contributes to Astrocyte-Mediated Retinal Ganglion Cell Protection |
title_full | Sigma 1 Receptor Contributes to Astrocyte-Mediated Retinal Ganglion Cell Protection |
title_fullStr | Sigma 1 Receptor Contributes to Astrocyte-Mediated Retinal Ganglion Cell Protection |
title_full_unstemmed | Sigma 1 Receptor Contributes to Astrocyte-Mediated Retinal Ganglion Cell Protection |
title_short | Sigma 1 Receptor Contributes to Astrocyte-Mediated Retinal Ganglion Cell Protection |
title_sort | sigma 1 receptor contributes to astrocyte-mediated retinal ganglion cell protection |
topic | Retinal Cell Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8819349/ https://www.ncbi.nlm.nih.gov/pubmed/35103752 http://dx.doi.org/10.1167/iovs.63.2.1 |
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