title: Effects of topical sphingosine-1-phosphate 1 receptor agonist on corneal allograft in mice.
abstract: OBJECTIVE
  The aim of this study was to compare the antirejection effects of topical selective sphingosine-1-phosphate 1 receptor (S1P1) agonist and cyclosporine A (CsA) on the acceptance of a transplanted, allogeneic cornea graft in a murine animal model.
  
  
  METHODS
  Fifty-six BALB/c mice were randomly divided into 4 groups. All the mice received corneal grafts from 28 C57BL/6 donors. Experimental recipients were treated with 0.25%, 0.5% S1P1 agonist suspension eye drops or 1% CsA eye drops 4 times a day after the corneal graft was performed. Controls received no treatment. The corneal grafts were imaged and evaluated with clinical scoring. The excised corneal sections 14 days after transplantation were stained using hematoxylin-eosin for histopathological evaluation. CD86+ and MHC-II+ dendritic cells in corneal samples were identified by immunohistochemical staining. The expression of mRNA in the cornea was evaluated using real-time quantitative PCR for interleukin-2, interferon-gamma, and cytotoxic T-lymphocyte antigen 4.
  
  
  RESULTS
  Corneal graft survival was prolonged by treatment with 0.5% S1P1 agonist and 1% CsA (P < 0.01, respectively) when compared with that in the control in clinical scoring. In addition, topical application of 0.5% S1P1 increased the cytotoxic T-lymphocyte antigen 4 mRNA expression of the corneal grafts. There were significant differences observed with 0.5% S1P1 and agonist 1% CsA (P < 0.01, respectively) when compared with the values of the control group in histology scoring.
  
  
  CONCLUSIONS
  Topical 0.5% S1P1 agonist is as effective as 1% CsA, and both can effectively prolong the survival of corneal allografts in mice.
authors.affiliation: *Department of Ophthalmology, Chinese People's Liberation Army General Hospital, Beijing, China; †Department of Ophthalmology, Chinese People's Liberation Army Air Force General Hospital, Beijing, China; and ‡Department of Ophthalmology, First Affiliated Hospital of Chinese People's Liberation Army General Hospital, Beijing, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Jia
authors.forename: Yong
authors.initials: Y
authors.lastname: Liu
authors.forename: Liqiang
authors.initials: L
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: Zhu
authors.forename: Yifei
authors.initials: Y
authors.lastname: Huang
mesh_terms: D000287:Administration, Topical; D064591:Allografts; D000818:Animals; D051940:B7-2 Antigen / Q000378:metabolism; D060908:CTLA-4 Antigen / Q000235:genetics; D003315:Cornea / Q000187:drug effects* / Q000378:metabolism; D016039:Corneal Transplantation; D016572:Cyclosporine / Q000494:pharmacology; D003713:Dendritic Cells / Q000378:metabolism; D000068876:Fingolimod Hydrochloride; D006084:Graft Rejection / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D007108:Immune Tolerance; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007371:Interferon-gamma / Q000235:genetics; D007376:Interleukin-2 / Q000235:genetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D009883:Ophthalmic Solutions; D011409:Propylene Glycols / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D049349:Receptors, Lysosphingolipid / Q000819:agonists*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D051940:B7-2 Antigen; D060908:CTLA-4 Antigen; C497965:Cd86 protein, mouse; D000949:Histocompatibility Antigens Class II; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D009883:Ophthalmic Solutions; D011409:Propylene Glycols; D012333:RNA, Messenger; D049349:Receptors, Lysosphingolipid; D007371:Interferon-gamma; D016572:Cyclosporine; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine