| アイテムタイプ |
学術雑誌論文 / Journal Article(1) |
| 公開日 |
2025-02-26 |
| 日付 |
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日付 |
2025-12-09 |
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日付タイプ |
Available |
| タイトル |
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タイトル |
Combination of blockade of endothelin signalling and compensation of IGF1 expression protects the retina from degeneration |
| 言語 |
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言語 |
eng |
| キーワード |
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主題Scheme |
Other |
|
主題 |
Retinitis pigmentosa |
| キーワード |
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主題Scheme |
Other |
|
主題 |
Prominin-1 |
| キーワード |
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主題Scheme |
Other |
|
主題 |
Insulin-like growth factor (IGF) |
| キーワード |
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主題Scheme |
Other |
|
主題 |
Gliosis |
| キーワード |
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|
主題Scheme |
Other |
|
主題 |
Mammalian/mechanical target of rapamycin (mTOR) |
| キーワード |
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主題Scheme |
Other |
|
主題 |
Adeno-associated virus (AAV) |
| キーワード |
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主題Scheme |
Other |
|
主題 |
Single-cell RNA sequencing (scRNA-seq) |
| 資源タイプ |
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資源タイプ |
journal article |
| アクセス権 |
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アクセス権 |
open access |
| 著者 |
Shigesada, Naoya
Shikada, Naoya
Shirai, Manabu
Toriyama, Michinori
Higashijima, Fumiaki
Kimura, Kazuhiro
Kondo, Toru
別所, 康全
篠塚, 琢磨
笹井, 紀明
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| 抄録 |
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内容記述タイプ |
Abstract |
|
内容記述 |
Retinitis pigmentosa (RP) and macular dystrophy (MD) cause severe retinal dysfunction, affecting 1 in 4000 people worldwide. This disease is currently assumed to be intractable, because effective therapeutic methods have not been established, regardless of genetic or sporadic traits. Here, we examined a RP mouse model in which the Prominin-1 (Prom1) gene was deficient and investigated the molecular events occurring at the outset of retinal dysfunction. We extracted the Prom1-deficient retina subjected to light exposure for a short time, conducted single-cell expression profiling, and compared the gene expression with and without stimuli. We identified the cells and genes whose expression levels change directly in response to light stimuli. Among the genes altered by light stimulation, Igf1 was decreased in rod photoreceptor cells and astrocytes under the light-stimulated condition. Consistently, the insulin-like growth factor (IGF) signal was weakened in light-stimulated photoreceptor cells. The recovery of Igf1 expression with the adeno-associated virus (AAV) prevented photoreceptor cell death, and its treatment in combination with the endothelin receptor antagonist led to the blockade of abnormal glial activation and the promotion of glycolysis, thereby resulting in the improvement of retinal functions, as assayed by electroretinography. We additionally demonstrated that the attenuation of mammalian/mechanistic target of rapamycin (mTOR), which mediates IGF signalling, leads to complications in maintaining retinal homeostasis. Together, we propose that combinatorial manipulation of distinct mechanisms is useful for the maintenance of the retinal condition. |
| 書誌情報 |
en : Cellular and Molecular Life Sciences
巻 81,
号 1,
発行日 2024-01-22
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| 出版者 |
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出版者 |
Springer |
| ISSN |
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収録物識別子タイプ |
EISSN |
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収録物識別子 |
1420-9071 |
| 出版者版DOI |
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関連タイプ |
isIdenticalTo |
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識別子タイプ |
DOI |
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関連識別子 |
https://doi.org/10.1007/s00018-023-05087-x |
| 出版者版URI |
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関連タイプ |
isIdenticalTo |
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識別子タイプ |
URI |
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関連識別子 |
https://link.springer.com/article/10.1007/s00018-023-05087-x |
| 権利 |
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権利情報Resource |
http://creativecommons.org/licenses/by/4.0/ |
|
権利情報 |
$00A9 The Author(s) 2024 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/. |
| 著者版フラグ |
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出版タイプ |
VoR |
fulltext (3.2 MB)
