| Project/Area Number |
17K16972
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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 |
Ophthalmology
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| Research Institution | Tokyo University of Science, Yamaguchi (2019)
Kyushu University (2017-2018) |
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Principal Investigator |
Kusunose Naoki 山陽小野田市立山口東京理科大学, 薬学部, 助教 (10725964)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | 時計遺伝子 / 網膜 / VEGF / 体内時計 / 血管新生 / 概日リズム |
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| Outline of Final Research Achievements |
Malfunction of clock genes, components of the molecular clock, is thought to increase the risk of numerous diseases including cancer. Vascular endothelial growth factor (VEGF) has a pivotal role in angiogenesis, and its expression levels are controlled by clock genes in tumor cells. Ophthalmic diseases such as age-related macular degeneration, proliferative diabetic retinopathy, and neovascular glaucoma are also associated with abnormal angiogenesis followed by upregulation of VEGF in the eye. Our present study partly uncovered the role of the clock gene DEC2 in retina, and our results suggest that disturbance of DEC2 expression induced by hypoxia might associate with exacerbation of VEGF-related retinal diseases. Hence, normalization of the circadian clock by mitigating associated risk factors with novel drugs might help to sustain retinal health and/or to reduce the severity of retinal disease.
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| Academic Significance and Societal Importance of the Research Achievements |
時計遺伝子はがん細胞における血管新生制御因子VEGFの発現制御に関与するため、時計遺伝子の働きによってがんの悪性度が一部規定されるといわれている。本研究では時計遺伝子が網膜におけるVEGFの発現調節に関与すること、すなわち、時計遺伝子が網膜においても疾患の発症に寄与することが明らかになった。このことから概日リズムの障害を回避することで網膜疾患の発症リスクを軽減できる可能性を示すことができた。
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