Functional analysis of the circadian photoreceptor melanopsin in diurnal and nocturnal species

2022 Fiscal Year Final Research Report

• Project/Area Number: 19H03266
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 44050:Animal physiological chemistry, physiology and behavioral biology-related
• Research Institution: Nagoya University (2020-2022); Keio University (2019)
• Principal Investigator: Hatori Megumi 名古屋大学, トランスフォーマティブ生命分子研究所, 特任准教授 (90590472)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 概日時計 / 光応答 / 環境応答 / 非視覚応答 / メラノプシン

Outline of Final Research Achievements

Melanopsin, expressed in a subset of retinal ganglion cells, mediates behavioral adaptation to ambient light and other non-image-forming photic responses. This has raised the possibility that pharmacological manipulation of melanopsin can modulate several central nervous system responses, including photophobia, sleep, circadian rhythms and neuroendocrine function. The discovery of melanopsin antagonist Opsinamide (Nat Chem Biol 2013) raised the prospect of therapeutic control of the melanopsin phototransduction system to regulate light-dependent and circadian clock-controlled behaviors and remediate pathological conditions both in nocturnal and diurnal species. In this study, novel compounds were developed. Previously unknown new in vivo functions of melanopsin were also discovered.

Free Research Field

動物生理

Academic Significance and Societal Importance of the Research Achievements

メラノプシンに作用する低分子化合物の開発に取り組み、阻害剤オプシナマイドを世界で初めて、そして現時点で唯一、報告した。今回新たに取り組んでいる新規化合物群とあわせ、薬理学的な調節は確立されたモデル動物以外でのメラノプシンの機能理解という目的においても強力であり、メラノプシンの新規機能発見につなげることが可能である。夜寝る直前のスマートフォン使用などで問題とされるブルーライト障害にメラノプシン関わっている。化合物は片頭痛や鬱などメラノプシン関連疾患の改善薬としてのポテンシャルも持ち、学術的だけではなく広く社会に意義を持つ。