title: Prolonging survival of corneal transplantation by selective sphingosine-1-phosphate receptor 1 agonist.
abstract: Corneal transplantation is the most used therapy for eye disorders. Although the cornea is somewhat an immune privileged organ, immune rejection is still the major problem that reduces the success rate. Therefore, effective chemical drugs that regulate immunoreactions are needed to improve the outcome of corneal transplantations. Here, a sphingosine-1-phosphate receptor 1 (S1P1) selective agonist was systematically evaluated in mouse allogeneic corneal transplantation and compared with the commonly used immunosuppressive agents. Compared with CsA and the non-selective sphingosine 1-phosphate (S1P) receptor agonist FTY720, the S1P1 selective agonist can prolong the survival corneal transplantation for more than 30 days with a low immune response. More importantly, the optimal dose of the S1P1 selective agonist was much less than non-selective S1P receptor agonist FTY720, which would reduce the dose-dependent toxicity in drug application. Then we analyzed the mechanisms of the selected S1P1 selective agonist on the immunosuppression. The results shown that the S1P1 selective agonist could regulate the distribution of the immune cells with less CD4+ T cells and enhanced Treg cells in the allograft, moreover the expression of anti-inflammatory cytokines TGF-β1 and IL-10 unregulated which can reduce the immunoreactions. These findings suggest that S1P1 selective agonist may be a more appropriate immunosuppressive compound to effectively prolong mouse allogeneic corneal grafts survival.
authors.affiliation: Department of Ophthalmology, Chinese PLA General Hospital. Beijing, China; Department of Ophthalmology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
authors.forename: Min
authors.initials: M
authors.lastname: Gao
authors.affiliation: Department of Ophthalmology, Chinese PLA Air Force General Hospital, Beijing, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Ophthalmology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Laboratory of Immunology, Institute of Basic Medical Sciences. Beijing, China.
authors.forename: Gencheng
authors.initials: G
authors.lastname: Han
authors.affiliation: Department of Ophthalmology, Chinese PLA General Hospital. Beijing, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Jia
authors.affiliation: Department of Ophthalmology, Chinese PLA General Hospital. Beijing, China.
authors.forename: Liqiang
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Ophthalmology, Chinese PLA General Hospital. Beijing, China.
authors.forename: Tian
authors.initials: T
authors.lastname: Lei
authors.affiliation: Department of Ophthalmology, Chinese PLA General Hospital. Beijing, China.
authors.forename: Yifei
authors.initials: Y
authors.lastname: Huang
mesh_terms: D000818:Animals; D016039:Corneal Transplantation; D016207:Cytokines / Q000097:blood; D000068876:Fingolimod Hydrochloride; D005786:Gene Expression Regulation / Q000187:drug effects; D006085:Graft Survival / Q000187:drug effects; D007249:Inflammation / Q000473:pathology; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008297:Male; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011409:Propylene Glycols / Q000494:pharmacology; D049349:Receptors, Lysosphingolipid / Q000819:agonists* / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives / Q000494:pharmacology; D013997:Time Factors
chemical_list: D016207:Cytokines; D011409:Propylene Glycols; D049349:Receptors, Lysosphingolipid; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine