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Investigation of the differentiation mechanism of ocular tissue-specific mast cells and its involvement in wound healing

Research Project

Project/Area Number 17K11453
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Ophthalmology
Research InstitutionKochi University

Principal Investigator

FUKUDA Ken  高知大学, 教育研究部医療学系臨床医学部門, 准教授 (70335751)

Co-Investigator(Kenkyū-buntansha) 石田 わか  高知大学, 医学部, 特任助教 (40761705)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsマスト細胞 / 組織特異性 / 線維芽細胞 / 結膜 / 創傷治癒 / 結膜線維芽細胞 / コラーゲンゲル / matrix metalloprotainase / ブレブ / 瘢痕化 / 濾過手術 / P2X7受容体 / 結合組織型マスト細胞 / 粘膜型マスト細胞 / アレルギー・ぜんそく / 細胞・組織
Outline of Final Research Achievements

Mast cells co-cultured with conjunctival fibroblasts showed increased expression of murine mast cell protease (Mcpt) 4 and 5 mRNA, and decreased expression of the ATP receptor P2X7 receptor mRNA compared to bone marrow-derived mast cells (BMMCs). These results suggest that conjunctival fibroblasts promoted the differentiation of BMMC into connective tissue mast cells.
Furthermore, mast cells promoted collagen gel contraction in the presence of conjunctival fibroblasts. Mast cells act on conjunctival fibroblasts to promote the activation of matrix metalloproteinase (MMP)-2 and the production of proMMP-9 resulting in the stimulation of collagen gel contraction.

Academic Significance and Societal Importance of the Research Achievements

マスト細胞は、結膜の固有の細胞である線維芽細胞と一緒に培養する事により結合組織型マスト細胞へ分化した。また線維芽細胞に作用して、蛋白分解酵素であるマトリックスメタロプロテアーゼ(MMP)の産生と活性化を促進させた。その結果、これらの細胞を含むコラーゲンゲルの収縮が促進された。この結果は緑内障手術後の濾過胞の収縮と関与すると考えられ、マスト細胞あるいはMMPを制御することで、術後成績の改善に繋がる可能性が示唆された。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (43 results)

All 2020 2019 2018 2017

All Journal Article (31 results) (of which Peer Reviewed: 16 results,  Open Access: 9 results) Presentation (11 results) (of which Int'l Joint Research: 7 results) Book (1 results)

  • [Journal Article] Amelioration of conjunctival giant papillae by dupilumab in patients with atopic keratoconjunctivitis2020

    • Author(s)
      Fukuda Ken、Ebihara Nobuyuki、Kishimoto Tatsuma、Fukushima Atsuki
    • Journal Title

      The Journal of Allergy and Clinical Immunology: In Practice

      Volume: 8 Issue: 3 Pages: 1152-1155

    • DOI

      10.1016/j.jaip.2019.10.011

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] アレルギー性結膜疾患2020

    • Author(s)
      福田 憲
    • Journal Title

      JOHNS

      Volume: 36 Pages: 347-350

    • Related Report
      2019 Annual Research Report
  • [Journal Article] アレルギー性結膜炎の免疫療法 -舌下免疫療法と経口免疫療法の可能性2020

    • Author(s)
      福田 憲
    • Journal Title

      あたらしい眼科

      Volume: 37 Pages: 383-387

    • Related Report
      2019 Annual Research Report
  • [Journal Article] 食物を利用したアレルギー性結膜炎の治療2020

    • Author(s)
      福田 憲
    • Journal Title

      アレルギーの臨床

      Volume: 40 Pages: 9-12

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Recurrent Optic Perineuritis as the First Manifestation of Relapsing Polychondritis2019

    • Author(s)
      Miura Yusaku、Fukuda Ken、Taniguchi Yoshinori、Komori Masahiro、Fukushima Atsuki
    • Journal Title

      Journal of Neuro-Ophthalmology

      Volume: 39 Issue: 4 Pages: 513-514

    • DOI

      10.1097/wno.0000000000000820

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Local allergic conjunctivitis: a phenotype of allergic conjunctivitis2019

    • Author(s)
      Yamana Y, Fukuda K, Ko R, Uchio E
    • Journal Title

      Int Ophthalmol

      Volume: 39 Issue: 11 Pages: 2539-2544

    • DOI

      10.1007/s10792-019-01101-z

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Therapeutic Effects of Intravitreously Administered Bacteriophage in a Mouse Model of Endophthalmitis Caused by Vancomycin-Sensitive or -Resistant Enterococcus faecalis2019

    • Author(s)
      Kishimoto Tatsuma、Ishida Waka、Fukuda Ken、Nakajima Isana、Suzuki Takashi、Uchiyama Jumpei、Matsuzaki Shigenobu、Todokoro Daisuke、Daibata Masanori、Fukushima Atsuki
    • Journal Title

      Antimicrobial Agents and Chemotherapy

      Volume: 63 Issue: 11

    • DOI

      10.1128/aac.01088-19

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Miscellaneous Ocular Symptoms in a Case of Relapsing Polychondritis2019

    • Author(s)
      Fukuda Ken、Kishimoto Tatsuma、Fukushima Atsuki
    • Journal Title

      Ocular Immunology and Inflammation

      Volume: - Issue: 2 Pages: 352-354

    • DOI

      10.1080/09273948.2019.1674892

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Periostin deletion suppresses late-phase response in mouse experimental allergic conjunctivitis2019

    • Author(s)
      Asada Y, Okano M, Ishida W, Iwamoto S, Fukuda K, Hirakata T, Tada N, Fukushima A, Ebihara N, Kudo A, Matsuda A.
    • Journal Title

      Allergology International

      Volume: 68 Issue: 2 Pages: 233-239

    • DOI

      10.1016/j.alit.2018.09.007

    • NAID

      130007633580

    • ISSN
      1323-8930, 1440-1592
    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development of conjunctivitis with a conjunctival proliferative lesion in a patient treated with dupilumab for atopic dermatitis2019

    • Author(s)
      Fukuda K, Ishida W, Kishimoto T, Fukushima A.
    • Journal Title

      Allergology International

      Volume: 68 Issue: 3 Pages: 383-384

    • DOI

      10.1016/j.alit.2018.12.012

    • NAID

      130007678526

    • ISSN
      1323-8930, 1440-1592
    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] アレルギー性結膜炎の定義と病型分類2019

    • Author(s)
      福田 憲
    • Journal Title

      臨床眼科

      Volume: 73 Pages: 16-20

    • Related Report
      2018 Research-status Report
  • [Journal Article] 低アレルゲン性スギ花粉アレルゲンを含む米によるアレルギー性結膜炎モデルマウスの経口免疫療法2019

    • Author(s)
      福田 憲、石田わか
    • Journal Title

      臨床免疫・アレルギー科

      Volume: 71 Pages: 1-5

    • Related Report
      2018 Research-status Report
  • [Journal Article] Unilateral serous retinal detachment with choroidal thickening as a first presenting sign of acute myeloid leukemia.2019

    • Author(s)
      Kishimoto T, Fukuda K, Nishiuchi T, Hayashi N, Fukushima A.
    • Journal Title

      American Journal of Ophthalmology Case Reports

      Volume: 14 Pages: 51-54

    • DOI

      10.1016/j.ajoc.2019.02.005

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Evaluation of offset of conjunctival hyperemia induced by a Rho-kinase inhibitor; 0.4% Ripasudil ophthalmic solution clinical trial.2019

    • Author(s)
      Sakamoto E, Ishida W , Sumi T, Kishimoto T, Tada K, Fukuda K, Yoneda T, Kuroiwa H, Terao E, Fujisawa Y, Nakakura S, Jian K, Okumichi H, Kiuchi Y, Fukushima A.
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 3755-3755

    • DOI

      10.1038/s41598-019-40255-9

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Recurrent optic perineuritis as the first manifestation of relapsing polychondritis.2019

    • Author(s)
      Miura Y, Fukuda K, Taniguchi Y, Komori M, Fukushima A.
    • Journal Title

      Journal of Neuro-Ophthalmology

      Volume: -

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] 免疫寛容2018

    • Author(s)
      福田 憲
    • Journal Title

      あたらしい眼科

      Volume: 35 Pages: 511-511

    • Related Report
      2018 Research-status Report
  • [Journal Article] 結膜炎2018

    • Author(s)
      福田 憲
    • Journal Title

      眼科ケア

      Volume: 20 Pages: 11-13

    • Related Report
      2018 Research-status Report
  • [Journal Article] 角膜炎2018

    • Author(s)
      福田 憲
    • Journal Title

      眼科ケア

      Volume: 20 Pages: 14-17

    • Related Report
      2018 Research-status Report
  • [Journal Article] ドライアイ2018

    • Author(s)
      福田 憲
    • Journal Title

      眼科ケア

      Volume: 20 Pages: 18-19

    • Related Report
      2018 Research-status Report
  • [Journal Article] 花粉症に対する免疫療法を中心に2018

    • Author(s)
      福田 憲
    • Journal Title

      アレルギー・免疫

      Volume: 25 Pages: 940-945

    • Related Report
      2018 Research-status Report
  • [Journal Article] アレルギー性結膜疾患2018

    • Author(s)
      福田 憲、熊谷直樹
    • Journal Title

      Monthly Book OCULISTA

      Volume: 65 Pages: 8-14

    • Related Report
      2018 Research-status Report
  • [Journal Article] Requirement of longer term antiviral therapy in patients with cytomegalovirus anterior uveitis with corneal endothelial cell damage2018

    • Author(s)
      Harada Y, Fukuda K, Nakahira A, Tada K, Sumi T, Fukushima A.
    • Journal Title

      Clinical Ophthalmology

      Volume: 12 Pages: 1311-1316

    • DOI

      10.2147/opth.s164184

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 眼の掻痒感2018

    • Author(s)
      福田 憲、熊谷直樹
    • Journal Title

      眼科

      Volume: 60 Pages: 1066-1070

    • Related Report
      2018 Research-status Report
  • [Journal Article] アレルギー性結膜疾患の診断と治療2018

    • Author(s)
      岸本達真、福田 憲
    • Journal Title

      臨床眼科

      Volume: 72 Pages: 70-73

    • Related Report
      2018 Research-status Report
  • [Journal Article] Oral Immunotherapy for Allergic Conjunctivitis Using Transgenic Rice Expressing Hypoallergenic Antigens.2018

    • Author(s)
      Fukuda K, Ishida W, Wakasa Y, Takagi H, Takaiwa F, Fukushima A.
    • Journal Title

      Cornea. 2018 Nov;37 Suppl 1:S67-S73.

      Volume: 37 Issue: 1 Pages: S67-S73

    • DOI

      10.1097/ico.0000000000001758

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Efficacy of oral immunotherapy with a rice-based edible vaccine containing hypoallergenic Japanese cedar pollen allergens for treatment of established allergic conjunctivitis in mice2018

    • Author(s)
      Fukuda Ken、Ishida Waka、Harada Yosuke、Wakasa Yuhya、Takagi Hidenori、Takaiwa Fumio、Fukushima Atsuki
    • Journal Title

      Allergology International

      Volume: 67 Issue: 1 Pages: 119-123

    • DOI

      10.1016/j.alit.2017.06.006

    • NAID

      130006322022

    • ISSN
      1323-8930, 1440-1592
    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] ドライアイと炎症2018

    • Author(s)
      福田憲
    • Journal Title

      あたらしい眼科

      Volume: 35 Pages: 65-66

    • Related Report
      2017 Research-status Report
  • [Journal Article] Cytokine expression and barrier disruption in human corneal epithelial cells induced by alarmin released from necrotic cells.2017

    • Author(s)
      Fukuda K, Ishida W, Miura Y, Kishimoto T, Fukushima A.
    • Journal Title

      Jpn J Ophthalmol

      Volume: 61 Issue: 5 Pages: 415-422

    • DOI

      10.1007/s10384-017-0528-7

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Contributions of Intreleukin-33 and TSLP in a papain-soaked contact lens-induced mouse conjunctival Inflammation model.2017

    • Author(s)
      Sugita J, Asada Y , Ishida W, Iwamoto S, Sudo K, Suto H, Matsunaga T, Fukuda K, Fukushima A, Yokoi N, Ohno T, Azuma M, Ebihara N, Saito H, Kubo M, Nakae S, Matsuda A.
    • Journal Title

      Immunity, Inflammation and Disease.

      Volume: 5(4) Issue: 4 Pages: 515-525

    • DOI

      10.1002/iid3.189

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Corneal Fibroblasts as Sentinel Cells and Local Immune Modulators in InfectiousKeratitis.2017

    • Author(s)
      Fukuda K, Ishida W, Fukushima A, Nishida T.
    • Journal Title

      Int J Mol Sci

      Volume: 18(9) Issue: 9 Pages: 1831-1831

    • DOI

      10.3390/ijms18091831

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] ドライアイ点眼の抗炎症作用2017

    • Author(s)
      福田憲
    • Journal Title

      眼科

      Volume: 59 Pages: 707-713

    • Related Report
      2017 Research-status Report
  • [Presentation] Therapeutic effects of intravitreous bacteriophage on Enterococcus faecalis endophthalmitis in mice2019

    • Author(s)
      Fukuda K, Kishimoto T, Ishida W, Suzuki T, Uchiyama J, Matsuzaki S, Daibata M, Fukushima A
    • Organizer
      ARVO 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 重症アレルギー性結膜疾患の病態と治療2019

    • Author(s)
      福田 憲、石田わか、岸本達真、中島勇魚、角 環、福島敦樹
    • Organizer
      第68回日本アレルギー学会学術大会 シンポジウム22
    • Related Report
      2019 Annual Research Report
  • [Presentation] 猫ひっかき病に伴う後眼部病変の臨床的特徴の検討2019

    • Author(s)
      福田 憲、溝渕朋佳、岸本達真、西内貴史、福島敦樹
    • Organizer
      第53回日本眼炎症学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 抗IL-4受容体α抗体により結膜巨大乳頭が縮小したアトピー性角結膜炎の2例2019

    • Author(s)
      福田 憲、海老原伸行、岸本達真、福島敦樹
    • Organizer
      第2回日本眼科アレルギー学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Therapeutic effects of intravitreous bacteriophage on Enterococcus faecalis endophthalmitis in mice.2019

    • Author(s)
      Fukuda K, Kishimoto T, Ishida W, Suzuki T, Uchiyama J, Matsuzaki S, Daibata M, Fukushima A.
    • Organizer
      ARVO 2019
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Therapeutic effects of bacteriophage φef24c-p2 on Enterococcus faecalis endophthalmitis in mice.2018

    • Author(s)
      Fukuda K, Kishimoto T, Ishida W, Suzuki T, Uchiyama J, Matsuzaki S, Daibata M, Fukushima A.
    • Organizer
      5th World Congress on Targeting Infectious Diseases, Targeting Phage & Antibiotic Resistance
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Characterization of ocular posterior segment involvement in Japanese patients with cat scratch disease2018

    • Author(s)
      Ken Fukuda, Tomoka Mizobuchi, Isana Nakajima, Atsuki Fukushima
    • Organizer
      36th World Ophthalmology Congress
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 医薬品としての ファージ療法の臨床の現状2018

    • Author(s)
      福田 憲
    • Organizer
      第7回ファージ研究会・2018年日本細菌学会関東支部インターラボセミナー合同大会
    • Related Report
      2018 Research-status Report
  • [Presentation] Immunotherapy for allergic conjunctivitis2017

    • Author(s)
      Ken Fukuda
    • Organizer
      The European Academy of Allergy and Clinical Immunology Congress 2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Mast cells promote collagen lattice contraction mediated by conjunctival fibroblasts by up-regulating matrix metalloproteinase production2017

    • Author(s)
      Tatsuma Kishimoto, Ken Fukuda, Waka Ishida, Atsuki Fukushima
    • Organizer
      The European Academy of Allergy and Clinical Immunology Congress 2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] The involvement of Interleukin-10 on the early-phase reaction in the experimental allergic conjunctivitis in a murine model2017

    • Author(s)
      Waka Ishida, Ken Fukuda, Yosuke Harada, Osamu Taguchi, Atsuki Fukushima.
    • Organizer
      The European Academy of Allergy and Clinical Immunology Congress 2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Book] 眼科診療ビジュアルラーニング2 眼炎症2018

    • Author(s)
      溝渕朋佳、福田 憲(分担)、編集:園田康平
    • Total Pages
      280
    • Publisher
      中山書店
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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