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Excessive Thyroid Hormone Signaling Induces Photoreceptor Degeneration in Mice
Rod and cone photoreceptors degenerate in inherited and age-related retinal degenerative diseases, ultimately leading to loss of vision. Thyroid hormone (TH) signaling regulates cell proliferation, differentiation, and metabolism. Recent studies have shown a link between TH signaling and retinal deg...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Society for Neuroscience
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10481642/ https://www.ncbi.nlm.nih.gov/pubmed/37596046 http://dx.doi.org/10.1523/ENEURO.0058-23.2023 |
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author | Ma, Hongwei Yang, Fan York, Lilliana R. Li, Shujuan Ding, Xi-Qin |
author_facet | Ma, Hongwei Yang, Fan York, Lilliana R. Li, Shujuan Ding, Xi-Qin |
author_sort | Ma, Hongwei |
collection | PubMed |
description | Rod and cone photoreceptors degenerate in inherited and age-related retinal degenerative diseases, ultimately leading to loss of vision. Thyroid hormone (TH) signaling regulates cell proliferation, differentiation, and metabolism. Recent studies have shown a link between TH signaling and retinal degeneration. This work investigates the effects of excessive TH signaling on photoreceptor function and survival in mice. C57BL/6, Thra1(−/−), Thrb2(−/−), Thrb(−/−), and the cone dominant Nrl(−/−) mice received triiodothyronine (T3) treatment (5–20 μg/ml in drinking water) for 30 d, followed by evaluations of retinal function, photoreceptor survival/death, and retinal stress/damage. Treatment with T3 reduced light responses of rods and cones by 50–60%, compared with untreated controls. Outer nuclear layer thickness and cone density were reduced by ∼18% and 75%, respectively, after T3 treatment. Retinal sections prepared from T3-treated mice showed significantly increased numbers of TUNEL-positive, p-γH2AX-positive, and 8-OHdG-positive cells, and activation of Müller glial cells. Gene expression analysis revealed upregulation of the genes involved in oxidative stress, necroptosis, and inflammation after T3 treatment. Deletion of Thra1 prevented T3-induced degeneration of rods but not cones, whereas deletion of Thrb2 preserved both rods and cones. Treatment with an antioxidant partially preserved photoreceptors and reduced retinal stress responses. This study demonstrates that excessive TH signaling induces oxidative stress/damage and necroptosis, induces photoreceptor degeneration, and impairs retinal function. The findings provide insights into the role of TH signaling in retinal degeneration and support the view of targeting TH signaling for photoreceptor protection. |
format | Online Article Text |
id | pubmed-10481642 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Society for Neuroscience |
record_format | MEDLINE/PubMed |
spelling | pubmed-104816422023-09-07 Excessive Thyroid Hormone Signaling Induces Photoreceptor Degeneration in Mice Ma, Hongwei Yang, Fan York, Lilliana R. Li, Shujuan Ding, Xi-Qin eNeuro Research Article: New Research Rod and cone photoreceptors degenerate in inherited and age-related retinal degenerative diseases, ultimately leading to loss of vision. Thyroid hormone (TH) signaling regulates cell proliferation, differentiation, and metabolism. Recent studies have shown a link between TH signaling and retinal degeneration. This work investigates the effects of excessive TH signaling on photoreceptor function and survival in mice. C57BL/6, Thra1(−/−), Thrb2(−/−), Thrb(−/−), and the cone dominant Nrl(−/−) mice received triiodothyronine (T3) treatment (5–20 μg/ml in drinking water) for 30 d, followed by evaluations of retinal function, photoreceptor survival/death, and retinal stress/damage. Treatment with T3 reduced light responses of rods and cones by 50–60%, compared with untreated controls. Outer nuclear layer thickness and cone density were reduced by ∼18% and 75%, respectively, after T3 treatment. Retinal sections prepared from T3-treated mice showed significantly increased numbers of TUNEL-positive, p-γH2AX-positive, and 8-OHdG-positive cells, and activation of Müller glial cells. Gene expression analysis revealed upregulation of the genes involved in oxidative stress, necroptosis, and inflammation after T3 treatment. Deletion of Thra1 prevented T3-induced degeneration of rods but not cones, whereas deletion of Thrb2 preserved both rods and cones. Treatment with an antioxidant partially preserved photoreceptors and reduced retinal stress responses. This study demonstrates that excessive TH signaling induces oxidative stress/damage and necroptosis, induces photoreceptor degeneration, and impairs retinal function. The findings provide insights into the role of TH signaling in retinal degeneration and support the view of targeting TH signaling for photoreceptor protection. Society for Neuroscience 2023-09-01 /pmc/articles/PMC10481642/ /pubmed/37596046 http://dx.doi.org/10.1523/ENEURO.0058-23.2023 Text en Copyright © 2023 Ma et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. |
spellingShingle | Research Article: New Research Ma, Hongwei Yang, Fan York, Lilliana R. Li, Shujuan Ding, Xi-Qin Excessive Thyroid Hormone Signaling Induces Photoreceptor Degeneration in Mice |
title | Excessive Thyroid Hormone Signaling Induces Photoreceptor Degeneration in Mice |
title_full | Excessive Thyroid Hormone Signaling Induces Photoreceptor Degeneration in Mice |
title_fullStr | Excessive Thyroid Hormone Signaling Induces Photoreceptor Degeneration in Mice |
title_full_unstemmed | Excessive Thyroid Hormone Signaling Induces Photoreceptor Degeneration in Mice |
title_short | Excessive Thyroid Hormone Signaling Induces Photoreceptor Degeneration in Mice |
title_sort | excessive thyroid hormone signaling induces photoreceptor degeneration in mice |
topic | Research Article: New Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10481642/ https://www.ncbi.nlm.nih.gov/pubmed/37596046 http://dx.doi.org/10.1523/ENEURO.0058-23.2023 |
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