Topical application of sphingosine 1-phosphate receptor 1 prolongs corneal graft survival in mice.

Abstract

The present study aimed to investigate the effects of topical application of sphingosine 1‑phosphate receptor 1 (S1P1) on allogeneic corneal transplantation in mice. A total of 45 BALB/c mice received corneal grafts from C57BL/6 donors. The recipients were randomly divided into three groups and treated with eye drops containing 0.5% S1P1, 1% cyclosporine A or saline as a negative control. The serum levels of interleukin (IL)‑2, IL‑10, tumor growth factor (TGF)‑β1 and interferon (IFN)‑γ were measured by ELISA. The numbers of CD4+ T cell and T‑regulatory (Treg) cell phenotypes were measured by flow cytometry. The cytokine mRNA expression was analyzed by quantitative polymerase chain reaction. The results demonstrated that corneal graft survival was prolonged in the S1P1 group [mean survival time (MST), 24.11±1.58 days], and 1% cyclosporine A (MST, 25.0±1.91 days) compared with the controls (MST, 13.44±0.48 days; P<0.01). S1P1 and cyclosporine A decreased CD4+ T‑cell levels (P<0.05) in the peripheral blood compared with those of the controls. However, an increase of CD4+ T cells in the spleen was noted in the S1P1 group (P<0.05) and Treg cells were also increased in the cervical lymph nodes in the S1P1 group (P<0.01). TGF‑β1 mRNA transcription in the corneal grafts increased following treatment with S1P1 (P<0.05) and TGF‑β1 in the serum following treatment with S1P1 also increased (P<0.01). In conclusion, S1P1 had a significant effect in corneal allograft rejection inhibition.