1995 Fiscal Year Final Research Report Summary
The Role of Cytokines and Cell Adhesion Molecules in Corneal Allograft Rejection.
| Project/Area Number |
06454495
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Ophthalmology
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| Research Institution | UNIVERSITY OF TOKYO |
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Principal Investigator |
TSURU Tadahiko University of Tokyo School of Medicine, Associate Professor, 医学部・附属病院, 助教授 (90126128)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAGAMI Satoru Jichi Medical School, Assistant Professor, 医学部, 講師
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| Project Period (FY) |
1994 – 1995
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| Keywords | Penetrating keratoplasty / Allograft rejection / Mouse / Cell adhesion molecule / Cytokines |
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| Research Abstract |
In order to clarify the role of cytokines and cell adhesion molecules in corneal allograft rejection, we developed an animal model of penetrating keratoplasty using mice. The penetrating keratoplasty was done with a trephine of 2.0 mm in diameter. BALB/c mice (H-2^k) were used for donor andrecipient in isografting experiment, and C3H/He (H-2^k) mice and BALB/c mice (H-2^k) were used for donor and recipient, respectively. All of the isografts remained transparent during the observation period. In contrast, the allografts were rejected in more than 90 % of the eyes. However, treatments by systemic administration of monoclonal antibodies to cell adhesion molecules including ICAM-1, LFA-1 and VLA-4 significantly suppressed the allograft rejection. Especially, combined use of anti-LFA-1 and anti-ICAM-1 antibodies or anti-LFA-1 and anti-VLA-4 antibodies highly suppressed the allograftrejection. The challenge tests demonstratedthat the immunosuppressive effects by the monoclonal antibodies to the cell adhesion molecules were alloantigen-specific. As a next step, we studied the role of cytokines in corneal allograft rejection by immunohistochemistry. Interleukin (IL)-2, interferon-gamma (IFN-gamma) and major histocompatibility complex (MHC) class II antigens were studies. In the allografted corneas, the IL-2, IFN-gamma and MHC class II antigens were positively stained in 7 days after penetrating keratoplasty. As a result of the research, it was demonstratedthat cell adhesion molecules and cytokines playda criticalrole in corneal allograft rejection in mice.
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