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  • Title: Significant prolongation of orthotopic corneal-graft survival in FTY720-treated mice.
    Author: Zhang EP, Müller A, Ignatius R, Hoffmann F.
    Journal: Transplantation; 2003 Nov 27; 76(10):1511-3. PubMed ID: 14657695.
    Abstract:
    BACKGROUND: The novel immunomodulator, FTY720, mainly acts through sequestering of lymphocytes to secondary lymphatic tissue, thereby suppressing their infiltration into grafted organs. This study aimed to investigate its influence on corneal-graft survival. METHODS: Sixteen BALB/c mice (H-2d) received corneal transplants from C3H (H-2k) mice. Eight mice were treated with FTY720 (10 mg/kg per day) orally from day -1 to day 11, and all animals received 0.1% dexamethasone eye drops for the same time. In addition, eyes and regional lymph nodes from similarly treated animals were subjected to immunohistochemistry and proliferation assays. RESULTS: FTY720 significantly prolonged graft survival from 28+/-8.1 to 36.5+/-7.1 days (P=0.021). In treated animals, corneal infiltration by CD4+ and F4/80+ cells was reduced from 70.8+/-60.3 to 7.0+/-9.0 (P=0.004) and from 97.5+/-30.7 to 44.8+/-24.9 (P=0.01) cells, respectively, and allogeneic T-cell proliferation was decreased. CONCLUSIONS: FTY720 treatment substantially protects corneal allografts and may provide an immunomodulatory strategy in clinical corneal transplantation.
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