Development of new glaucoma therapy other than decreasing intraocular pressure

• Project/Area Number: 25462750
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Ophthalmology
• Research Institution: Akita University
• Principal Investigator: Yoshitomi Takeshi 秋田大学, 医学(系)研究科(研究院), 教授 (60191623)
• Co-Investigator(Kenkyū-buntansha): ISHIKAWA Makoto 秋田大学, 大学院医学系研究科, 准教授 (10212854)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 緑内障 / 眼循環 / 血管平滑筋 / 薬理学 / 炭酸脱水酵素阻害 / 緑内障治療薬 / 眼循環改善効果 / 視野進行

Outline of Final Research Achievements

Topically applied carbonic anhydrase inhibitor can increase optic disc blood flow in rabbit which was assessed using laser speckle flowgraphy analyzer. Further, we investigate the direct pharmacological effect of acetazolamide and dorzolamide on isolated ciliary arterial smooth muscle. Acetazolamide had little effect compared with dorzolamide on isolated rabbit ciliary arteries in vitro using isometric tension recording method. Those results indicate that carbonic unhydrase inhibitor increase optic nerve blood flow with different pharmacological mechanisms from decreasing intraocular pressure Jpn J Ophthalmol. 2016;60:103-10）.

Research Products

• [Journal Article] Dorzolamide-induced relaxation of isolated rabbit ciliary arteries mediated by inhibition of extracellular calcium influx. (2016)
  • Author(s): Dong, Y., Sawada, Y., Cui, J., Hayakawa, M., Ogino, D., Ishikawa, M., & Yoshitomi, T.
  • Journal Title: Japanese Journal of Ophthalmology Volume: 60(2) Issue: 2 Pages: 103-110
  • DOI: 10.1007/s10384-015-0423-z
  • Peer Reviewed / Open Access
• [Journal Article] Insulin Resistance Is a Risk Factor for Increased Intraocular Pressure: The Hisayama Study. (2015)
  • Author(s): Fujiwara K, Yasuda M, Ninomiya T, Hata J, Hashimoto S, Yoshitomi T, Kiyohara Y, Ishibashi T.
  • Journal Title: Invest Ophthalmol Vis Sci. Volume: 56 Issue: 13 Pages: 7983-7987
  • DOI: 10.1167/iovs.15-16766
  • Peer Reviewed / Open Access
• [Journal Article] Lamina Cribrosa Depth Variation Measured by Spectral-Domain Optical Coherence Tomography Within and Between Four Glaucomatous Optic Disc Phenotypes. (2015)
  • Author(s): Sawada Y, Hangai M, Murata K, Ishikawa M, Yoshitomi T.
  • Journal Title: Invest Ophthalmol Vis Sci. Volume: 56 Issue: 10 Pages: 5777-5784
  • DOI: 10.1167/iovs.14-15942
  • Peer Reviewed / Open Access
• [Journal Article] Experimentally Induced Mammalian Models of Glaucoma. (2015)
  • Author(s): Ishikawa M, Yoshitomi T, Zorumski CF, Izumi Y.
  • Journal Title: Biomed Res Volume: 281214 Pages: 1-11
  • DOI: 10.1155/2015/281214
  • Peer Reviewed / Open Access
• [Journal Article] Structure and function of the interphotoreceptor matrix surrounding retinal photoreceptor cells (2015)
  • Author(s): Ishikawa M、 Sawada Y、 Yoshitomi T
  • Journal Title: Experimental Eye Research Volume: 133 Pages: 3-18
  • DOI: 10.1016/j.exer.2015.02.017
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Neurosteroids are endogenous neuroprotectants in an ex vivo glaucoma model (2014)
  • Author(s): ④ Ishikawa M、 Yoshitomi T、 Zorumski CF、 Izumi Y
  • Journal Title: Investigative Ophthalmology & Visual Science Volume: 55 Issue: 12 Pages: 8531-8541
  • DOI: 10.1167/iovs.14-15624
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The effects of prostaglandin analogues on intracellular Ca2+ in ciliary arteries of wild-type and prostanoid receptor-deficient mice. (2013)
  • Author(s): Abe S, Watabe H, Takaseki S, Aihara M, Yoshitomi T.
  • Journal Title: J Ocul Pharmacol Ther. Volume: 29 Issue: 1 Pages: 55-60
  • DOI: 10.1089/jop.2011.0197
  • Peer Reviewed
• [Journal Article] Abnormalities in glutamate metabolism and excitotoxicity in the retinal diseases. (2013)
  • Author(s): Ishikawa M.
  • Journal Title: Scientifica (Cairo) Volume: 2013
  • Peer Reviewed
• [Presentation] Insulin resistance is a risk factor for the elevation of intraocular pressure: the Hisayama Study (2015)
  • Author(s): Fujiwara K, Yasuda M, Ninimiya T, Hata J, Hashimoto S, Ikeda Y, Yoshitomi T, Kiyohara Y, Ishibashi T
  • Organizer: The 8th Joint Meeting of JAPAN-CHINA-KOREA Ophthalmologists.
  • Place of Presentation: Fukuoka,
  • Year and Date: 2015-10-17
  • Int'l Joint Research
• [Presentation] LSFGを用いたウサギ眼血流と摘出毛様動脈平滑筋の収縮弛緩に及ぼすRhoキナーゼ阻害薬リパスジルの影響. (2015)
  • Author(s): 太田悠介, 高関早苗, 吉冨健志：
  • Organizer: 第26回日本緑内障学会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-09-11
• [Presentation] Upregulation of neurosteroid synthesizing enzyme in an ex vivo rat glaucoma model. (2015)
  • Author(s): Ishikawa M, Yoshitomi T, Izumi Y
  • Organizer: The 6th world glaucoma congress.
  • Place of Presentation: Hong Kong
  • Year and Date: 2015-06-06
  • Int'l Joint Research
• [Presentation] Lamina cribrosa anterior surface depth and morphology in normal eyes. (2015)
  • Author(s): Sawada Y, Ishikawa M, Fujiwara K, Yoshitomi T
  • Organizer: The 6th world glaucoma congress.
  • Place of Presentation: Hong Kong
  • Year and Date: 2015-06-06
  • Int'l Joint Research
• [Presentation] 炭酸脱水酵素阻害剤の眼動脈平滑筋に対する効果の検討（第２報） (2014)
  • Author(s): 渡辺 駿，董 雅儒，高関早苗，吉冨健志
  • Organizer: 第25回日本緑内障学会
  • Place of Presentation: 岐阜
  • Year and Date: 2014-09-13 – 2014-09-14
• [Presentation] Effects of Histamine on Rabbit Ciliary Artery (2014)
  • Author(s): Dai Ogino, Shun Watanabe, Yusuke Ohta, Kota Fujiwara, Takeshi Yoshitomi
  • Organizer: World Ophthalmology Congress 2014－APAO2014－118ｔｈ JOS
  • Place of Presentation: 東京
  • Year and Date: 2014-04-04 – 2014-04-07
• [Presentation] Pressure-dependent changes of glutamate transporters in the ex vivo rat retinal preparation (2014)
  • Author(s): Makoto Ishikawa, Takeshi Yoshitomi, and Yukitoshi Izumi
  • Organizer: World Ophthalmology Congress 2014－APAO2014－118ｔｈ JOS
  • Place of Presentation: 東京
  • Year and Date: 2014-04-04 – 2014-04-07
• [Presentation] Effects of Calcitonin Gene Related Peptide on Bovine Trabecular Meshwork and Ciliary Muscle (2013)
  • Author(s): Dai Ogino, Shun Watanabe, Yusuke Ohta, Kota Fujiwara, Takeshi Yoshitomi．
  • Organizer: Association for Research in Vision and Ophthalmology 2013
  • Place of Presentation: Seatle, USA
• [Presentation] Setting target pressure and selection of initial therapy (2013)
  • Author(s): Takeshi Yoshitomi．
  • Organizer: World Glaucoma Congress
  • Place of Presentation: Vancouver Canada
  • Invited
• [Presentation] Pressure-dependent changes of GLT-1 splice variants in the isolated rat retinal preparation. (2013)
  • Author(s): Ishikawa, M., Yoshitomi, T., Izumi, Y.
  • Organizer: World Glaucoma Congress
  • Place of Presentation: Vancouver Canada
• [Presentation] 眼圧に影響を与える血管病変危険因子の検討：久山町研究 (2013)
  • Author(s): １） 藤原康太，安田美穂，池田康博，橋本佐和子，朝隈朋子，荒川聡，吉冨健志，岩瀬愛子，新家眞，清原祐，石橋達郎．
  • Organizer: 第67回日本臨床眼科学会
  • Place of Presentation: 横浜
• [Book] 今日の治療指針2015. (2015)
  • Author(s): 吉冨健志
  • Total Pages: 1973
  • Publisher: 医学書院