Study of conceal burrier function and application for regenerative medicine

• Project/Area Number: 25670731
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Ophthalmology
• Research Institution: Osaka University
• Principal Investigator: Tsujikawa Motokazu 大阪大学, 医学(系)研究科(研究院), 寄附講座教授 (70419472)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 膠様滴状角膜ジストロフィ / TACSTD2 / 再生医療 / 遺伝子治療 / モデル動物 / 膠様滴状角膜ジストロフィー / ノックアウトマウス / バリア機能 / 角膜上皮 / タイトジャンクション / 疾患モデル動物

Outline of Final Research Achievements

Cornea is important tissue which function is burrier function and it must keep transparency. Gelatinous drop-like corneal dystrophy (GDLD) is severe corneal dystrophy in which burrier function is disrupted and patients are suffered from corneal opacity. We have successfully identified the responsible gene for GDLD, TACSTD2. We made knock out mouse line of TACSTD2 and obtained corneal opacity phenotype like in human. Aged mouse (over 1 year) showed significant increased frequency of sever corneal opacity in TACSTD2 knock out. We have successfully cultured the corneal epithelium cells from the mouse and try to develop the new therapy that is the combination therapy of regenerative medicine and gene therapy.

Research Products

• [Journal Article] Co-ordinated ocular development from hiPSCs and recovery of anterior eye function. (2016)
  • Author(s): Hayashi R, Ishikawa Y, Sasamoto Y, Katori R, Nomura N, Ichikawa T, Araki S, Soma T, Kawasaki S, Sekiguchi K, Quantock A, Tsujikawa M, & Nishida K.
  • Journal Title: Nature Volume: 17;531(7594) Issue: 7594 Pages: 376-80
  • DOI: 10.1038/nature17000
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] A missense variant in FGD6 confers increased risk of polypoidal choroidal vasculopathy. (2016)
  • Author(s): Huang L, Zhang H, Cheng CY, Wen F, Tam PO, Zhao P, Chen H, et al
  • Journal Title: Nature Genetics Volume: In Press
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] PAX6 Isoforms, along with Reprogramming Factors, Differentially Regulate the Induction of Cornea-specific Genes. (2016)
  • Author(s): Sasamoto Y, Hayashi R, Park S, Saito-Adachi M, Suzuki Y, Kawasaki S, Quantock A, Nakai K, Tsujikawa M, and Nishida K
  • Journal Title: Scientific Reports Volume: 22;6:20807 Issue: 1 Pages: 20807-20807
  • DOI: 10.1038/srep20807
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Relationship between Corneal Guttae and Quality of Vision in Patients with Mild Fuchs' Endothelial Corneal Dystrophy. (2015)
  • Author(s): Watanabe S, Oie Y, Fujimoto H, Soma T, Koh S, Tsujikawa M, Maeda N, Nishida K.
  • Journal Title: Ophthalmology. Volume: 122 Issue: 10 Pages: 2103-9
  • DOI: 10.1016/j.ophtha.2015.06.019
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Quantitative regional differences in corneal endothelial abnormalities in the central and peripheral zones in Fuchs' endothelial corneal dystrophy (2014)
  • Author(s): Fujimoto H, Maeda N, Soma T, Oie Y, Koh S, Tsujikawa M, Nishida K
  • Journal Title: Invest Ophthalmol Vis Sci. Volume: 55 Pages: 5090-8
  • Peer Reviewed / Open Access
• [Journal Article] Identification and potential application of human corneal endothelial progenitor cells (2014)
  • Author(s): Hara S, Hayashi R, Soma T, Kageyama T, Duncan T, Tsujikawa M, Nishida K
  • Journal Title: Stem Cells Dev Volume: 2014 Pages: 2190-201
  • Peer Reviewed / Open Access
• [Journal Article] Development of a cell sheet transportation technique for regenerative medicine (2014)
  • Author(s): Oie Y, Nozaki T, Takayanagi H, Hara S, Hayashi R, Takeda S, Mori K, Moriya N, Soma T, Tsujiakwa M, Saito K, Nishida K
  • Journal Title: Tissue Eng Part C Methods. Volume: 20 Pages: 373-82
  • Peer Reviewed / Open Access
• [Journal Article] Maintenance and distribution of epithelial stem/progenitor cells after corneal reconstruction using oral mucosal epithelial cell sheets. (2014)
  • Author(s): Soma T, Hayashi R, Sugiyama H, Tsujikawa M, Kanayama S, Oie Y, Nishida K.
  • Journal Title: PLoS One. Volume: 9 Issue: 10 Pages: e110987-e110987
  • DOI: 10.1371/journal.pone.0110987
  • Peer Reviewed / Open Access
• [Journal Article] Ocular forward light scattering and corneal backward light scattering in patients with dry eye (2014)
  • Author(s): Shizuka Koh, Naoyuki Maeda, Chikako Ikeda, Sanae Asonuma, Hayato Mitamura, Yoshinori Oie, Takesh Soma, Motokazu Tsujikawa, Satoshi Kawasaki, Kohji Nishida
  • Journal Title: Invest Ophthalmol Vis Sci Volume: 55 Issue: 10 Pages: 6601-6606
  • DOI: 10.1167/iovs.14-15125
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Rigid gas-permeable contact lens-assisted cataract surgery in patients with severe keratoconus. (2014)
  • Author(s): Oie Y, Kamei M, Matsumura N, Fujimoto H, Soma T, Koh S, Tsujikawa M, Maeda N, Nishida K.
  • Journal Title: J Cataract Refract Surg. Volume: 40 Issue: 3 Pages: 345-348
  • DOI: 10.1016/j.jcrs.2014.01.001
  • Peer Reviewed
• [Journal Article] Identification and Potential Application of Human Corneal Endothelial Progenitor Cells. (2014)
  • Author(s): 1． Hara S, Hayashi R, Soma T, Kageyama T, Duncan T, Tsujikawa M, Nishida K.
  • Journal Title: Stem Cells Dev Volume: In press
  • Peer Reviewed
• [Journal Article] Development of a Cell Sheet Transportation Technique for Regenerative Medicine. (2013)
  • Author(s): Oie Y, Nozaki T, Takayanagi H, Hara S, Hayashi R, Takeda S, Mori K, Moriya N, Soma T, Tsujikawa M, Saito K, Nishida K.
  • Journal Title: Tissue Eng Part C Methods. Volume: - Pages: 373-82
  • Peer Reviewed
• [Journal Article] The role of the Nrf2-mediated defense system in corneal epithelial wound healing (2013)
  • Author(s): Hayashi R, Himori N, Taguchi K, Ishikawa Y, Uesugi K, Ito M, Duncan T, Tsujikawa M, Nakazawa T, Yamamoto M, Nishida K
  • Journal Title: Free Radic Biol Med Volume: 61C Pages: 333-342
  • DOI: 10.1016/j.freeradbiomed.2013.04.008
  • Peer Reviewed
• [Journal Article] Validation of Na,K-ATPase pump function of corneal endothelial cells for corneal regenerative medicine. (2013)
  • Author(s): 5． Hatou S, Higa K, Inagaki E, Yoshida S, Kimura E, Hayashi R, Tsujikawa M,Tsubota K, Nishida K, Shimmura S.
  • Journal Title: Tissue Eng Part C Methods Volume: 19 Issue: 12 Pages: 901-10
  • DOI: 10.1089/ten.tec.2013.0030
  • Peer Reviewed
• [Presentation] Corneal Dystrophies in Japan (2016)
  • Author(s): Tsujikawa M
  • Organizer: APAO 2016 (Asis Pacific association of Ophthalmology)
  • Place of Presentation: Taipei Taiwan
  • Year and Date: 2016-03-24
  • Int'l Joint Research / Invited
• [Presentation] Corneal Dystrophies in Japan (2016)
  • Author(s): Tsujikawa M
  • Organizer: World Ophthalmology Conference (WOC 2016)
  • Place of Presentation: Mexico Guadarahara
  • Year and Date: 2016-02-06
  • Int'l Joint Research / Invited
• [Presentation] 角膜再生医療の夜明け (2014)
  • Author(s): 辻川元一
  • Organizer: 日本眼科学会総会
  • Place of Presentation: 東京国際フォーラム
  • Year and Date: 2014-04-04
  • Invited
• [Presentation] Stem Cell Reserch in Corneal Endothelium (2014)
  • Author(s): Motokazu Tsujikawa
  • Organizer: 世界眼科学会
  • Place of Presentation: 東京国際フォーラム
  • Year and Date: 2014-04-03
  • Invited
• [Presentation] 角膜再生医療の幕開け (2014)
  • Author(s): 辻川元一
  • Organizer: 日本眼科学会総会
  • Place of Presentation: 東京
  • Invited
• [Presentation] Stem Cell Reserach in Corneal Endothelium (2014)
  • Author(s): Motokazu Tsujikawa
  • Organizer: 世界眼科学会
  • Place of Presentation: 東京
  • Invited
• [Book] 眼手術学４．角膜結膜屈折矯正 (2013)
  • Author(s): 辻川元一,臼井智彦,井上幸次,西田幸二,島崎潤,稲富勉,宮田和典,後藤浩,江口秀一郎,横井則彦,外園千恵,不二門尚
  • Total Pages: 513
  • Publisher: 文光堂