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Cell biological study on the stimulation of tissue stem cells of lacrimal glands of aged mammals.

Research Project

Project/Area Number 18K09431
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56060:Ophthalmology-related
Research InstitutionNational Defense Medical College

Principal Investigator

Ito Masataka  防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究施設、病院並びに防衛, 再生発生学, 准教授 (30534896)

Co-Investigator(Kenkyū-buntansha) 竹内 大  防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究施設、病院並びに防衛, 眼科学, 教授 (40260939)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords涙腺 / 組織幹細胞 / 加齢 / PD-1 / ノックアウトマウス / マイボーム腺 / ペルオキシソーム増殖因子活性化受容体γ / PPARγ / TRP channels / ハーダー腺 / 炎症 / 自然炎症 / サイトカイン
Outline of Final Research Achievements

In this project, we have performed following studies. (1) Histopathological observations of lacrimal gland tissues from aged humans and mice. In aged lacrimal gland tissues, mild chronic inflammatory changes with lymphocytes infiltration in both humans and mice and tissue destruction/remodeling by so-called “Harderinization” in mice were observed. (2) Cell culture study using Meibomian gland epithelial cells with a PPARγ agonist rosiglitazone (RSG). Lipid synthesis was stimulated by RSG. (3) Analyses of phenotypes of lacrimal gland in PD-1 knockout mice. PD-1 is an immune checkpoint molecule and this mutant mouse shows various autoimmune-related phenotypes such as nephritis and arthritis. We showed that severe inflammatory changes and Harderinization in lacrimal gland in this mouse as they aged. However, tissue regeneration of functional lacrimal gland was not observed.

Academic Significance and Societal Importance of the Research Achievements

高度な高齢化が進むわが国においてドライアイで悩む高齢者は多い。ドライアイ症状の有無は生活の質に直結することから、高齢者のドライアイ症状を改善することはわが国の福祉の向上に大いに資するものといえる。本研究は、これに対して再生医学の観点からのアプローチを試みた基礎研究である。
人体器官の多くでは障害が生じると再生機転が働いて障害部位は再生される。例えば皮膚ではその再生能力は終生維持されることが知られているが、皮膚と同様の発生学的な起源をもちながらも涙腺では皮膚ほどの旺盛な再生能は持たないことが本研究における幾つかの実験で明らかとなった。再生涙腺の臨床応用にはさらなる知見の蓄積が必要と考えられた。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (19 results)

All 2021 2020 2019 Other

All Int'l Joint Research (3 results) Journal Article (8 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 8 results,  Open Access: 4 results) Presentation (8 results)

  • [Int'l Joint Research] Queen's University Belfast(英国)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] Friedrich-Alexander Universitat(ドイツ)

    • Related Report
      2019 Research-status Report
  • [Int'l Joint Research] Friedrich-Alexander-Universitat Erlangen(ドイツ)

    • Related Report
      2018 Research-status Report
  • [Journal Article] Programmed Cell Death-1 Pathway Deficiency Enhances Autoimmunity Leading to Dacryoadenitis of Mice.2021

    • Author(s)
      Sakurai Y, Usui Y, Hattori T, Takeuchi M, Takayama K, Karasawa Y, Nishio Y, Yamakawa N, Saitoh D, Goto H, Ito M.
    • Journal Title

      Am J Pathol

      Volume: in press Issue: 6 Pages: 1077-1093

    • DOI

      10.1016/j.ajpath.2021.02.014

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Microglia increase tight-junction permeability in coordination with M?ller cells under hypoxic condition in an in vitro model of inner blood-retinal barrier2021

    • Author(s)
      Inada Makoto、Xu Heping、Takeuchi Masaru、Ito Masataka、Chen Mei
    • Journal Title

      Experimental Eye Research

      Volume: 205 Pages: 108490-108490

    • DOI

      10.1016/j.exer.2021.108490

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Identification of Lacrimal Gland Postganglionic Innervation and Its Regulation of Tear Secretion.2020

    • Author(s)
      Kai Jin, Toshihiro Imada, Ryuji Hisamura, Masataka Ito, Haruki Toriumi, Kenji F Tanaka, Shigeru Nakamura & Kazuo Tsubota
    • Journal Title

      The American Journal of Pathology

      Volume: 190 Issue: 5 Pages: 1068-1079

    • DOI

      10.1016/j.ajpath.2020.01.007

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A New Modified Experimental Meibomian Gland Injury Model: Partial Loss of Gland Due to Orifice Cauterization and the Alleviating Potential of 22-Oxacalcitriol2020

    • Author(s)
      Jin Kai、Kawashima Motoko、Ito Masataka、Arita Reiko、Sano Kokoro、Tsubota Kazuo
    • Journal Title

      Journal of Clinical Medicine

      Volume: 10 Issue: 1 Pages: 6-6

    • DOI

      10.3390/jcm10010006

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Retinal changes in mice spontaneously developing diabetes by Th17-cell deviation2020

    • Author(s)
      Taguchi M, Someya H, Inada M, Nishio Y, Takayama K, Harimoto K, Karasawa Y, Ito M, Takeuchi M.
    • Journal Title

      Exp Eye Res.

      Volume: 198 Pages: 108155-108155

    • DOI

      10.1016/j.exer.2020.108155

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ペルオキシソーム増殖因子活性化受容体γの活性化による培養マイボーム腺細胞の分化2020

    • Author(s)
      唐沢容子、伊藤正孝、西尾佳明、竹内大
    • Journal Title

      日本眼科学会雑誌

      Volume: 124 Pages: 7-14

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Corneal Sensory Experience via Transient Receptor Potential Vanilloid 1 Accelerates the Maturation of Neonatal Tearing2019

    • Author(s)
      Jin Kai、Imada Toshihiro、Nakamura Shigeru、Izuta Yusuke、Oonishi Erina、Shibuya Michiko、Sakaguchi Hisayo、Tanabe Hirotaka、Ito Masataka、Katanosaka Kimiaki、Tsubota Kazuo
    • Journal Title

      The American Journal of Pathology

      Volume: 189 Issue: 9 Pages: 1699-1710

    • DOI

      10.1016/j.ajpath.2019.05.015

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Protective effects of dexamethasone on hypoxia-induced retinal edema in a mouse model2019

    • Author(s)
      Inada Makoto、Taguchi Manzo、Harimoto Kohzou、Karasawa Yoko、Takeuchi Masaru、Ito Masataka
    • Journal Title

      Experimental Eye Research

      Volume: 178 Pages: 82-90

    • DOI

      10.1016/j.exer.2018.09.014

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Presentation] リパスジルの実験的自己免疫性ぶどう膜網膜炎に対する抗炎症作用の検討2020

    • Author(s)
      播本 幸三,西尾 佳明,唐沢 容子,伊藤 正孝,竹内 大
    • Organizer
      日本眼科学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 低酸素環境下における網膜グリア細胞のタイトジャンクションに及ぼす影響2020

    • Author(s)
      稲田 真,竹内 大,伊藤 正孝,唐沢 容子,西尾 佳明
    • Organizer
      日本眼科学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] インターフェロンガンマ欠損Akita マウスに発症した糖尿病性網膜症2019

    • Author(s)
      田口 万藏, 西尾 佳明, 稲田 真, 高山 圭, 播本 幸三, 唐沢 容子, 伊藤 正孝, 竹内 大
    • Organizer
      第123回日本眼科学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] 糖尿病網膜症を発症する IFN-g 欠損 Akita マウスの免疫メカニズム解析2019

    • Author(s)
      竹内 大, 田口 万藏, 西尾 佳明, 稲田 真, 高山 圭, 播本 幸三, 唐沢 容子, 伊藤 正孝
    • Organizer
      第123回日本眼科学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] ペルオキシソーム増殖因子活性化受容体 g 活性化による培養マイボーム腺細胞の分化2019

    • Author(s)
      唐沢容子, 伊藤正孝, 西尾佳明, 竹内大
    • Organizer
      第123回日本眼科学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] Programmed cell death-1 遺伝子欠損マウスに生じる涙腺炎の原因解析2019

    • Author(s)
      櫻井裕, 伊藤 正孝, 竹内 大
    • Organizer
      第123回日本眼科学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] マウスにおけるハーダー腺とハーダー腺化涙腺の比較検討2019

    • Author(s)
      伊藤正孝、平柳淑恵、今城純子
    • Organizer
      第124回日本解剖学会総会・全国学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] ペルオキシソーム増殖因子活性化受容体γ活性化による培養マイボーム腺細胞の分化2019

    • Author(s)
      唐沢 容子、伊藤 正孝、竹内 大
    • Organizer
      第123回日本眼科学会総会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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