Prediction of diurnal IOP variation by polymorphisms in clock genes in normal tension glaucoma

• Project/Area Number: 16K11262
• 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: Higashide Tomomi 金沢大学, 附属病院, 講師 (20291370)
• Research Collaborator: Morokado Satomi ; Nakazawa Kazuki ; Tsuchiya Shunsuke ; Sugiyama Kazuhisa
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 緑内障 / 眼圧 / 日内変動 / コンタクトレンズセンサー / 時計遺伝子 / 遺伝子多型 / 眼圧日内変動 / 概日リズム

Outline of Final Research Achievements

Diurnal variation of intraocular pressure (IOP) was evaluated with a contact lens sensor (CLS) in untreated patients with primary open angle glaucoma. The acrophase of cosine-fitted CLS curve was negatively associated with visual field sensitivity. The CLS parameters combined with an IOP value measured the day before CLS measurements were useful for predicting the diurnal IOP variation. The mean arterial pressure was positively correlated with CLS value. Among 17 single nucleotide polymorphisms in 7 clock genes, rs 2304672 in PER2 gene was associated with the acrophase of the cosine-fitted CLS curve.

Academic Significance and Societal Importance of the Research Achievements

本研究によって広義原発開放隅角緑内障においてコンタクトレズセンサーによる眼圧日内変動測定は緑内障診療に有用な情報を提供できる可能性があること、コンタクトレズセンサー測定値の変動パターンに時計遺伝子であるPER2の遺伝子多型が関連していることを明らかにすることができた。これらにより、時計遺伝子が緑内障眼の眼圧日内変動に及ぼす影響についてさらに解明していくことが緑内障診療において非常に重要であることを示すことができた。

Research Products

• [Journal Article] Effects of Trabeculectomy on Waveform Changes of Laser Speckle Flowgraphy in Open Angle Glaucoma. (2019)
  • Author(s): Takeshima S, Higashide T, Kimura M, Udagawa S, Yamada Y, Takemoto D, Ohkubo S, Sugiyama K.
  • Journal Title: Invest Ophthalmol Vis Sci. Volume: 60 Issue: 2 Pages: 677-684
  • DOI: 10.1167/iovs.18-25694
  • Peer Reviewed / Open Access
• [Journal Article] The Relationship Between Interocular Asymmetry of Visual Field Defects and Optic Nerve Head Blood Flow in Patients With Glaucoma. (2019)
  • Author(s): Yamada Y, Higashide T, Udagawa S, Takeshima S, Sakaguchi K, Nitta K, Sugiyama K.
  • Journal Title: J Glaucoma Volume: 28 Issue: 3 Pages: 231-237
  • DOI: 10.1097/ijg.0000000000001181
  • Peer Reviewed
• [Journal Article] Effects of ripasudil, a rho kinase inhibitor, on blood flow in the optic nerve head of normal rats. (2019)
  • Author(s): Wada Y, Higashide T, Nagata A, Sugiyama K.
  • Journal Title: Graefes Arch Clin Exp Ophthalmol. Volume: 257 Issue: 2 Pages: 303-311
  • DOI: 10.1007/s00417-018-4191-6
  • Peer Reviewed
• [Presentation] Influence of blood pressure and other factors on 24-hour contact lens sensor measurements in patients with untreated glaucoma (2019)
  • Author(s): Kazuki Nakazawa, Tomomi Higashide, Shunsuke Tsuchiya, Satomi Morokado, Masahiko Okayama, Kazuhisa Sugiyama
  • Organizer: 8th World Glaucoma Congress
  • Int'l Joint Research
• [Presentation] SENSIMED Triggerfish; as adjunct to tonometry to identify primary open angle glaucoma patients with measured intraocular pressure below the diagnostic threshold. (2018)
  • Author(s): Satomi Morokado, Tomomi Higashide, Sonja Simon-Zoula, Thierry Varidel, Kazuhisa Sugiyama
  • Organizer: 33rd Asia-Pacific Academy of Ophthalmology Congress
  • Int'l Joint Research
• [Presentation] 原発性開放隅角緑内障（狭義）の診断補助としてのTriggerfish®の有用性 (2018)
  • Author(s): 諸角聡美, 東出朋巳, 土屋俊輔, Sonja Simon-Zoula, Thierry Varidel, 杉山和久
  • Organizer: 第122回日本眼科学会総会
• [Presentation] 緑内障患者における眼圧日内変動と２４時間血圧の関連 (2018)
  • Author(s): 中澤 和樹、東出 朋巳、土屋 俊輔、諸角 聡美、杉山 和久
  • Organizer: 第29回日本緑内障学会
• [Presentation] 無治療緑内障眼の眼圧日内変動に対するコンタクトレンズ型センサーの有用性 (2017)
  • Author(s): 諸角聡美, 東出朋巳, 土屋俊輔, 杉山和久
  • Organizer: 第71回日本臨床眼科学会
• [Presentation] SENSIMED Triggerfish as Adjunct to Tonometry to Identify Primary Open Angle Glaucoma Patients With Measured Intraocular Pressure Below the Diagnostic Threshold (2017)
  • Author(s): Morokado S, Higashide T, Simon Zoula S, Sugiyama K, Tsuchiya S, Varidel T
  • Organizer: The 33rd Asia-Pacific Academy of Ophthalmology (APAO) Congress
  • Int'l Joint Research