Detecting the circadian oscillator of the murine intraocular pressure rhythm

• Project/Area Number: 17K11420
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Ophthalmology
• Research Institution: Kanazawa University
• Principal Investigator: Sugiyama Kazuhisa 金沢大学, 医学系, 教授 (80179168)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 緑内障 / 体内時計 / 眼圧日内変動 / 視交叉上核 / オプシン グルココルチコイド / オプシン / サーカディアンリズム / 時計遺伝子

Outline of Final Research Achievements

The iris/ciliary body complex expressed Opn4 and Opn5 mRNA; however, unlike in retina and cornea, neither the iris-CB complex nor the co-cultured complex was directly entrained by light-dark cycle in vitro. The diurnal IOP change of Opn4-/-;rd1/rd1 mice showed an antiphasic pattern to wild-type mice and their rhythms followed the whole-animal behavioral rhythm. In addition, glucocorticoid, the hormone secreted from the adrenal gland, plays an important role in creating the murine circadian IOP rhythm.

Academic Significance and Societal Importance of the Research Achievements

上記の研究成果により、マウスの眼圧日内変動は体内中枢時計であるSCNによってそのリズムはコントロールされ、SCNから日内変動形成に至るまでのシグナル伝達には副腎皮質ホルモンであるグルココルチコイドが大きな役割を果たしていることを初めて報告した。この知見により、今後グルココルチコイドをターゲットとした眼圧日内変動コントロールを試み、最終的には緑内障の新規治療薬へと繋がっていく可能性がある。

Research Products

• [Journal Article] Effect of inhalation anesthesia with isoflurane on circadian rhythm of murine intraocular pressure. (2021)
  • Author(s): Tsuchiya S, Higashide T, Hatake S, Sugiyama K.
  • Journal Title: Experimental Eye Research. Volume: 203 Pages: 108420-108420
  • Peer Reviewed
• [Journal Article] The Role of Beta-Adrenergic Receptors in the Regulation of Circadian Intraocular Pressure Rhythm in Mice. (2017)
  • Author(s): Tuchiya S,Higashide T,Toida K,Sugiyama K
  • Journal Title: Curr Eye Res. Volume: 42(7) Pages: 1013-1017
• [Journal Article] Light entrainment of the murine intraocular presure circadian rhythm utilizes non-local mechanisms. (2017)
  • Author(s): Tuchiya S,Buhr ED,Higashide T,Sugiyama K,Van Gelder RN
  • Journal Title: Plos One. Volume: 12(9)
• [Presentation] マウス眼圧日内変動におけるイソフルラン吸入麻酔の影響 (2021)
  • Author(s): 土屋俊輔、東出朋巳、杉山和久.
  • Organizer: 第125回日本眼科学会総会
• [Presentation] 吸入麻酔薬(2%イソフルラン)下マウス眼圧測定の有用性：眼圧日内変動における検討. (2019)
  • Author(s): 土屋俊輔、東出朋巳、杉山和久.
  • Organizer: 第30回日本緑内障学会
• [Presentation] Effects of glaucocorticoid on the murine intraocular pressure circadian rhythm (2018)
  • Author(s): 土屋俊輔
  • Organizer: 第122回日本眼科学会総会
• [Presentation] Visual field changes after vitrectomy for epiretinal membranes in glaucoma (2018)
  • Author(s): 土屋俊輔
  • Organizer: 23rd International Visual Field & Imaging Symposium
  • Int'l Joint Research
• [Presentation] 10-2視野セクター別解析による緑内障眼の黄斑上膜術後視野変化の検討 (2018)
  • Author(s): 土屋俊輔
  • Organizer: 第72回日本臨床眼科学会
• [Presentation] Mechanisms of light entrainment of the mammalian ciliary body circadian clock. (2017)
  • Author(s): 土屋俊輔
  • Organizer: ARVO2017
  • Int'l Joint Research