Significant prolongation of orthotopic corneal-graft survival in FTY720-treated mice

Transplantation. 2003 Nov 27;76(10):1511-3. doi: 10.1097/01.TP.0000086344.04487.4F.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology
  • Corneal Transplantation / immunology*
  • Fingolimod Hydrochloride
  • Graft Survival / drug effects
  • Graft Survival / immunology*
  • Immunosuppressive Agents / therapeutic use
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C3H
  • Propylene Glycols / therapeutic use*
  • Sphingosine / analogs & derivatives
  • Transplantation, Homologous

Substances

  • Immunosuppressive Agents
  • Propylene Glycols
  • Fingolimod Hydrochloride
  • Sphingosine