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MOLECULAR MECHANISMS OF CORNEAL WOUND HEALING AFTER PHOTO-REFRACTIVE CORNEAL SURGERY

Research Project

Project/Area Number 11557127
Research Category

Grant-in-Aid for Scientific Research (B).

Allocation TypeSingle-year Grants
Section展開研究
Research Field Ophthalmology
Research InstitutionDeparmtnent of Ophthalmology, Yamagata University School of Medicine

Principal Investigator

YAMASHITA Hidetoshi  Professor, Deparmtnt of Ophthalmology, Yamagata University School of Medicine, 医学部・眼科学, 教授 (90158163)

Co-Investigator(Kenkyū-buntansha) KONNO Nobuhiko  Instructor, Deparmtnt of Ophthalmology, Yamagata University School of Medicine, 医学部・眼科学, 助手
TERASHIMA Kazuhito  Instructor, Deparmtnt of Ophthalmology, Yamagata University School of Medicine, 医学部・眼科学, 助手 (30280895)
TAKAHASHI Yoshinori  Assistant Professor , Deparmtnt of Ophthalmology, Yamagata University School of Medicine, 医学部・眼科学, 講師 (20236334)
川崎 良  山形大学, 医学部・附属病院・眼科, 助手 (70301067)
笠木 靖夫  山形大学, 医学部・眼科学, 助手 (60250924)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥13,500,000 (Direct Cost: ¥13,500,000)
Fiscal Year 2000: ¥6,700,000 (Direct Cost: ¥6,700,000)
Fiscal Year 1999: ¥6,800,000 (Direct Cost: ¥6,800,000)
KeywordsExcimer Laser / Cornea / Refractive Surgery / extracellular matrix / cytokines / TGF-β / hyalutonan / intracellular signal transduction / 屈折矯正手術 / コラーゲン / hsp47 / TGF-βシグナル伝達 / ステロイド療法
Research Abstract

After photo-refractive surgery, the corneal wound healing process occurs. Suring this process, the scar is formed and disturbs vision. In this study, we used the corneal wound healing after excimer laser keratectomy model to investigate the new extracellular matrix(ECM)formation. Our focus in this study is the role(s)of transforming growth factor-β(TGF-β)in the ECM formation in wound healing. TGF-β exerts its effects through two types of serine/threonine kinase receptors (type II and I receptors), which activate Smad family signal transducers. Using the cultured cells derived bovine cornea, TGF-β stimulated ECM protein production and hyaluronan synthase(HAS)activity through the pathways including TGF-β receptors and Smad family transducers. In the wound healing process in the excimer laser abrasion model, the corneal epithelial cells surrounding the wound proliferated, migrated and covered the abraded area. Under the regenerated epithelium, keratocytes first disappeared and then re-pop … More ulated the anterior corneal stroma and were involved in the formation of subepithelial ECM formation. In this process, the keratocytes were activated and recruited into the wound site. The activated keratocytes and abnormal ECM thereafter disappeared during tissue remodelling. During the wound healing process, the expression of 3 TGF-β isoforms(TGF-β1, β2, β3), 2 types of TGF-β receptors, Smad family members increased in the regenerating epithelium and the activated keratocytes, which shows that TGF-β is produced and affects wound healing process through the pathways including Smads. These responses were blocked by the treatment with the antibodies neutralizing TGF-β. Blocking effects by antibody to TGF-β1 was modt significant among the isoforms. Taken together, it is spechlated the TGF-β1 is the main player to activate and recruit the keratocytes to produce ECM in the corneal stroma after excimer laser keratectomy, and the functions are different among 3 isoforms. This process was correlated directly with TGF-β, of which the mechanisms remains to be resolved. Less

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (19 results)

All Other

All Publications (19 results)

  • [Publications] Usui T,Yamashita H et al.: "Expression regulation of hyaluro nan synthase in corneal endothelial cells."Invest Ophthalmal Vis Sci. 41. 3261-3267 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Obata H,Yamashita H et al.: "Expression of TGF-β superfamily receptors in rat eyes."Acta Ophthalmal. 77. 151-156 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Mita T,Yamashita H et al: "Functional difference of TGF-β isoforms regulating corneal wound healing after excimer laser keratectomy."Exp Eye Res. 68. 513-519 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kaji Y,Yamashita H et al: "Effects of anti-inflammatory agents on corneal wound healing process after excimer laser keratectomy."J Cat Ref Surg. 26. 426-431 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 山下英俊,臼井智彦 他: "「平滑筋細胞学」-結合組織のシグナル伝達"メジカルセンス社. 8 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Obata H, Kaji Y, Yamada H, Kato M, Tsuru T,Yamashita H: "Expression of transforming growth factor-β superfamily receptors in rat eye"Acta Ophthalmol. 77. 151-156 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Mita T Yamashita H , Kaji Y , Obata H, Hanyu A, Suzuki M, Tobari I: "Functional difference of TGF-β isoforms regulating corneal wound healing after excimer laser keratectomy"Exp Eye Res. 68. 513-519 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kaji Y, Amano S, Oshika T, Obata H, Ohashi T, Sakai H, Shirasawa E, Tsuru T, Yamashita H: "Effects of anti-inflammatory agents on corneal wound-healing process after surface excimer laser keratectomy"J Cat Ref Surg. 26. 426-431 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Usui T, Amano S, Oshika T, Suzuki K, Miyata K, Araie M,Heldin P,Yamashita H: "Expression regulation of hyaluronan synthase(HAS)in corneal endothelial cells"Invest Ophthalmol Vis Sci. 41. 3261-3267 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Usui T.Yamashita H et al.: "Expression regulation of hyaluronan synthase in corneal endothelial cells"Invest Ophthalmal Vis Sci. 41. 3261-3267 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Obata H.Yamashita H et al.: "Expression of TGF-βsuperfamily receptors in rat eyes"Acta Ophthalmal. 77. 151-156 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Mita T.Yamashita H et al.: "Functional difference of TGF-βisoforms regulating corneal wound healing after excimer laser keratectomy"Exp Eye Res. 68. 513-519 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kaji Y.Yamashita H et al: "Effects of auti-inflammatory agents on corneal wound healing process after excimer laser keratectomy"J Cat Ref Sung. 26. 426-431 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 山下英俊,臼井智彦 他: "「平滑筋細胞学」-結合組織のシグナル伝達"メジカルセンス社(分担). 8 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Usui T, Yamashita H et al: "Hyaluronan synthase expression in bovine eyes."Invest Ophthalmol Vis Sci. 40. 563-567 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Obata H, Yamashita H et al: "Expression of TGF-β superfamily receptors in rat eye."Acta Ophthalmol. 77. 151-156 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Mita T, Yamashita H et al: "Functional difference of TGF-β isoforms reglulating corneal wound healing after excimer laser keratectomy."Exp Eye Res. 68. 513-519 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kaji Y, Yamashita H et al: "Effects of anti-inflammatory ageuts on corneal wound healing process after swface exciwer laser heratectomy."J Cat Ref Surg. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] 山下英俊他: "平滑筋細胞学"結合組織のシグナル伝達:TGF-β(分担執筆). 101〜108 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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