Retinal imaging for axonal transport in glaucoma optic neuropathy

• Project/Area Number: 19K22682
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 56:Surgery related to the biological and sensory functions and related fields
• Research Institution: University of Fukui
• Principal Investigator: Inatani Masaru 福井大学, 学術研究院医学系部門, 教授 (40335245)
• Project Period (FY): 2019-06-28 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000); Fiscal Year 2021: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2020: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 緑内障

Outline of Research at the Start

緑内障は、網膜神経節細胞の軸索(視神経)がダメージを受け、細胞生存に必要な物質の軸索輸送が停止することにより、細胞死を起こし、失明する。本研究の目的は、緑内障における軸索輸送の時間空間的変化を無侵襲かつライブイメージで観察し、その病態をあきらかにすることである。我々は、眼科診療機器である光干渉断層計(OCT)で、軸索輸送されるミトコンドリアが観察出来る画期的な実験マウスであるYFP-Thy1-mito-トランスジェニックマウスを独自に作成した。このマウスを用いて、軸索内を輸送されるミトコンドリアが、緑内障でどのように分布変化するのかを無侵襲かつ経時的に観察する。

Outline of Final Research Achievements

We have successfully observed mitochondria distributed in the optic nerve of the mouse retina noninvasively with a medical confocal scanning diode laser ophthalmoscope using our originally generated YFP-Thy1-mito transgenic mice. When glaucoma occurred in mice, mitochondria in the optic nerve were shown to shrink in size and decrease in number within the optic nerve axon, while maintaining a uniform distribution. Retinal ganglion cells were found to undergo cell death after the preceding reduction in mitochondrial size and number.

Academic Significance and Societal Importance of the Research Achievements

本研究は、既存の医療機器を用いて、無侵襲で、網膜におけるミトコンドリアの分布を観察できた点に、学術的意義がある。眼球は透明な組織で構成されており、中枢神経組織である網膜における神経機能を光を用いて観察できるという点で大きなアドバンテージがあると言える。緑内障は日本人の失明原因のトップに位置する疾患であり、視神経が非可逆に障害される前段階の視神経の機能を明らかにすることで、緑内障の早期発見早期治療に役立てられる社会的意義がある。

Research Products

• [Journal Article] Application of moving particle semi-implicit (MPS) method on retro-oil fluid using three-dimensional vitreous cavity models from magnetic resonance imaging (2022)
  • Author(s): Gozawa Makoto、Watanabe Naoki、Iwasaki Kentaro、Takamura Yoshihiro、Inatani Masaru
  • Journal Title: Scientific Reports Volume: 12 Issue: 1 Pages: 1735-1735
  • DOI: 10.1038/s41598-022-05886-5
  • Peer Reviewed / Open Access
• [Journal Article] Intermitochondrial signaling regulates the uniform distribution of stationary mitochondria in axons (2022)
  • Author(s): Matsumoto Nozomu、Hori Ikuma、Kajita Masashi K.、Murase Tomoya、Nakamura Wataru、Tsuji Takahiro、Miyake Seiji、Inatani Masaru、Konishi Yoshiyuki
  • Journal Title: Molecular and Cellular Neuroscience Volume: 119 Pages: 103704-103704
  • DOI: 10.1016/j.mcn.2022.103704
  • Peer Reviewed / Open Access
• [Journal Article] Long-Term Outcomes of a Kahook Dual Blade Procedure Combined with Phacoemulsification in Japanese Patients with Open-Angle Glaucoma (2022)
  • Author(s): Iwasaki Kentaro、Kakimoto Hiroshi、Orii Yusuke、Arimura Shogo、Takamura Yoshihiro、Inatani Masaru
  • Journal Title: Journal of Clinical Medicine Volume: 11 Issue: 5 Pages: 1354-1354
  • DOI: 10.3390/jcm11051354
  • Peer Reviewed / Open Access
• [Journal Article] Prospective study of corneal endothelial cell loss after trabeculectomy (2021)
  • Author(s): Iwasaki Kentaro、Arimura Shogo、Takamura Yoshihiro、Inatani Masaru
  • Journal Title: Acta Ophthalmologica Volume: 99 Issue: 4
  • DOI: 10.1111/aos.14561
  • Peer Reviewed
• [Journal Article] Comparison of 5-year outcomes between trabeculectomy combined with phacoemulsification and trabeculectomy followed by phacoemulsification: a retrospective cohort study (2021)
  • Author(s): Arimura Shogo、Iwasaki Kentaro、Orii Yusuke、Takamura Yoshihiro、Inatani Masaru
  • Journal Title: BMC Ophthalmology Volume: 21 Issue: 1 Pages: 188-188
  • DOI: 10.1186/s12886-021-01949-9
  • Peer Reviewed / Open Access
• [Journal Article] Performances of glaucoma operations with Kahook Dual Blade or iStent combined with phacoemulsification in Japanese open angle glaucoma patients. (2020)
  • Author(s): Iwasaki K, Takamura Y, Orii Y, Arimura S, Inatani M.
  • Journal Title: International Journal of Ophthalmology Volume: 13 Issue: 6 Pages: 941-945
  • DOI: 10.18240/ijo.2020.06.13
  • Peer Reviewed / Open Access
• [Journal Article] Clinical practice preferences for glaucoma surgery in Japan: a survey of Japan Glaucoma Society specialists. (2020)
  • Author(s): Iwasaki K, Arimura S, Takamura Y, Inatani M
  • Journal Title: Japanese Journal of Ophthalmology Volume: 64 Issue: 4 Pages: 385-391
  • DOI: 10.1007/s10384-020-00749-w
  • Peer Reviewed
• [Journal Article] Oxytocin induced epithelium-mesenchimal transition through Rho-ROCK pathway in ARPE-19 cells, a human retinal pigmental cell line (2020)
  • Author(s): Tsuji Takahiro、Inatani Masaru、Tsuji Chiharu、Cheranov Stanislav M.、Kadonosono Kazuaki
  • Journal Title: Tissue and Cell Volume: 64 Pages: 101328-101328
  • DOI: 10.1016/j.tice.2019.101328
  • Peer Reviewed
• [Journal Article] Conjunctival structure of glaucomatous eyes treated with anti-glaucoma eye drops: a cross-sectional study using anterior segment optical coherence tomography. (2020)
  • Author(s): Gozawa M, Takamura Y, Iwasaki K, Arimura S, Inatani M
  • Journal Title: BMC Ophthalmology Volume: 20 Issue: 1 Pages: 244-244
  • DOI: 10.1186/s12886-020-01518-6
  • Peer Reviewed / Open Access
• [Journal Article] Filtering Blebs after Baerveldt Glaucoma Implantation Using Magnetic Resonance Imaging: A Prospective Investigation. (2020)
  • Author(s): wasaki K, Kanamoto M, Arimura S, Takamura Y, Kimura H, Inatani M
  • Journal Title: Ophthalmology Glaucoma Volume: 3 Issue: 3 Pages: 221-224
  • DOI: 10.1016/j.ogla.2020.01.003
  • Peer Reviewed / Open Access
• [Journal Article] Evaluation of deep convolutional neural networks for glaucoma detection. (2019)
  • Author(s): Phan S, Satoh S, Yoda Y, Kashiwagi K, Oshika T, Japan Ocular Imaging Registry Research Group.
  • Journal Title: Jpn J Ophthalmol. Volume: Feb 24 Issue: 3 Pages: 276-283
  • DOI: 10.1007/s10384-019-00659-6
  • Peer Reviewed / Open Access
• [Journal Article] Prospective Cohort Study on Refractive Changes after Trabeculectomy. (2019)
  • Author(s): Iwasaki K, Takamura Y, Arimura S, Tsuji T, Matsumura T, Gozawa M, Inatani M.
  • Journal Title: J Ophthalmol. Volume: 1 Pages: 4731653-4731653
  • DOI: 10.1155/2019/4731653
  • Peer Reviewed / Open Access
• [Journal Article] Relationship between Vision-Related Quality of Life and Central 10° of the Binocular Integrated Visual Field in Advanced Glaucoma. (2019)
  • Author(s): Yamazaki Y, Sugisaki K, Araie M, Murata H, Kanamori A, Inoue T, Ishikawa S, Yoshikawa K, Maeda H, Yamada Y, Negi A, Inatani M, Tanihara H, Okinami S, Mizuki K, Mishima K, Uchida K, Matsumoto S.
  • Journal Title: Sci Rep. Volume: 9 Issue: 1 Pages: 14990-14990
  • DOI: 10.1038/s41598-019-50677-0
  • Peer Reviewed / Open Access
• [Journal Article] Trabeculectomy followed by phacoemulsification versus trabeculectomy alone: The Collaborative Bleb-Related Infection Incidence and Treatment Study. (2019)
  • Author(s): Arimura S, Iwasaki K, Gozawa M, Takamura Y, Inatani M.
  • Journal Title: PLoS One. Volume: 14 Issue: 10 Pages: e0223439-e0223439
  • DOI: 10.1371/journal.pone.0223439
  • Peer Reviewed / Open Access
• [Presentation] Combined iStent trabecular micro-bypass and cataract surgery in Japanese glaucomatous eyes. (2021)
  • Author(s): Inatani M
  • Organizer: 5th Asia-Pacific Glaucoma Congress
  • Int'l Joint Research
• [Presentation] Treatment strategies for neovascular glaucoma in the new era. (2021)
  • Author(s): Inatani M
  • Organizer: The Chinese University of Hong Kong Virtual Grandround
  • Int'l Joint Research / Invited
• [Presentation] How to create the excellent filtering bleb in Baerveldt glaucoma implantation. シンポジウム18 Hot topics: Glaucoma treament (2020)
  • Author(s): 稲谷 大
  • Organizer: 第74回日本臨床眼科学会
• [Presentation] 緑内障神経保護アップデート (2020)
  • Author(s): 稲谷 大
  • Organizer: 第275回長野県眼科医会集談会
  • Invited
• [Remarks] 福井大学眼科学教室
  • URL: http://ganka-fukuimed.jp
• [Remarks] 福井大学眼科学教室
  • URL: http://www.med.u-fukui.ac.jp/GANKA/
• [Remarks] 福井大学医学部眼科学教室
  • URL: http://ganka-fukuimed.jp