Analysis of regulatory mechanism in retinal circadian rhythm
| Project/Area Number |
17K15574
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Environmental physiology(including physical medicine and nutritional physiology)
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| Research Institution | Aichi Medical University (2018)
Kindai University (2017) |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | 網膜 / 概日時計 / 光応答反応 / 視交叉上核 / コルチコステロン / 光感受性 / 活動リズム / 光位相反応 / 時差ぼけ / 松果体 / メラトニン / 環境生理 |
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| Outline of Final Research Achievements |
The retina transmits light signals to entrain the central circadian clock in the suprachiasmatic nucleus (SCN). Although the SCN regulates the peripheral circadian physiological function, the detail in the retina remains unclear since ambient light is also involved. We first found circadian sensory system to light in the inner retina. Its phase was shifted slowly like the SCN in jet lag, and its pattern were disrupted by adrenalectomy and rescued by glucocorticoid administration, indicating that the SCN rather than ambient light regulates retinal rhythm through glucocorticoid. Expression analysis of neurotransmitter-related genes revealed that diurnal change of GABArelated gene in the RGC mediate retinal photosensitivity rhythm, which is disrupted by retina specific clock deletion. Thus, SCN may regulate GABA-mediated photosensitivity rhythm. This study first demonstrates the entrainment regulatory pathway of retinal circadian rhythm by the SCN.
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| Academic Significance and Societal Importance of the Research Achievements |
網膜からの光情報は概日中枢である視交叉上核に伝達され、体全体の体内時計を統御している。網膜概日リズムは、視交叉上核から誘導された同調因子だけでなく強い同調因子、すなわち環境光の入力も受けるので同調機構は不明のままであったが、本研究により視交叉上核由来の因子が優位であることが判明した。これは、わずかなまたは不規則な光刺激が中枢時計と網膜時計との間の内部非同期を誘発し、視交叉上核へ光信号が不安定になる問題を回避するシステムであると考えられる。さらに、主観的昼にのみ光感受性を低下させる概日リズムの詳細も判明したが、これは昼の日光から網膜が変性して細胞死を起こさないように目を保護すると考えられる。
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Report
(3 results)
Research Products
(12 results)
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[Journal Article] Identification of circadian clock modulators from existing drugs2018
Author(s)
T. Katherine Tamai, Yusuke Nakane, Wataru Ota, Akane Kobayashi, Masateru Ishiguro, Naoya Kadofusa, Keisuke Ikegami, Kazuhiro Yagita, Yasufumi Shigeyoshi, Masaki Sudo, Taeko Nishiwaki-Ohkawa, Ayato Sato, & Takashi Yoshimura
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Journal Title
EMBO Molecular Medicine
Volume: -
Issue: 5
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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