Influence of clock gene on angiogenesis in retina

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K16972
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Ophthalmology
• Research Institution: Tokyo University of Science, Yamaguchi (2019); Kyushu University (2017-2018)
• 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)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 時計遺伝子 / 網膜

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.

Free Research Field

時間生物学

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。