2000 Fiscal Year Final Research Report Summary
MOLECULAR MECHANISMS OF CORNEAL WOUND HEALING AFTER PHOTO-REFRACTIVE CORNEAL SURGERY
| Project/Area Number |
11557127
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Ophthalmology
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| Research Institution | Deparmtnent of Ophthalmology, Yamagata University School of Medicine |
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Principal Investigator |
YAMASHITA Hidetoshi Professor, Deparmtnt of Ophthalmology, Yamagata University School of Medicine, 医学部・眼科学, 教授 (90158163)
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| 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)
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| Project Period (FY) |
1999 – 2000
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| Keywords | Excimer Laser / Cornea / Refractive Surgery / extracellular matrix / cytokines / TGF-β / hyalutonan / intracellular signal transduction |
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| 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
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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
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