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Effects of Topical Sphingosine-1-Phosphate 1 Receptor Agonist on Corneal Allograft in Mice

Jia, Liang MD; Liu, Yong MD; Wang, Liqiang MD; Zhu, Jing MD; Huang, Yifei MD

doi: 10.1097/ICO.0000000000000077
Basic Investigation

Purpose: 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.

*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.

Reprints: Yifei Huang, Department of Ophthalmology, Chinese PLA General Hospital, Beijing, China 100853 (e-mail:

Supported by the National Natural Science Foundation of China (No. 81170830) and the National Key Basic Research and Development plan (No. 2013CB967001).

The authors have no other funding or conflicts of interest to disclose.

Received November 08, 2013

Accepted December 28, 2013

Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved.