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Topical application of FTY720 and cyclosporin A prolong corneal graft survival in mice.
Mol Vis 2012; 18:624-33MV

Abstract

PURPOSE

To investigate the effects of topical FTY720 and cyclosporin A (CsA) on allogeneic corneal transplantation in mice.

METHODS

A total of 75 BALB/c mice received corneal grafts from C57BL/6 donors. Recipients were treated with 0.1%, 0.3%, or 0.5% FTY720 ophthalmic gel or 1% CsA eye-drops after the graft (controls received no treatment). The number of cluster of differentiation (CD)4+ T cells and CD4+CD25+forkhead box P3 (Foxp3)+ regulatory (Treg) cell phenotypes were measured by flow cytometry. Cytokine mRNA expression in corneal grafts was analyzed by real-time quantitative PCR. CD4 + T cells and cytokines in corneal samples were identified by immunohistochemical staining.

RESULTS

Corneal graft survival was prolonged by treatment with topical 0.5% FTY720 (mean survival time [MST], 24.1±1.6 days) or 1% CsA eye-drops (MST 25.0±1.9 days) compared with controls (MST, 13.4±0.5 days; n=9, both p<0.01). Topical 0.5% FTY720 treatment significantly increased the percentages of CD4 + T (p<0.05) and Treg cells (p<0.01; n=5) in the cervical lymph nodes compared with controls. Transforming growth factor-β1 (TGF-β1) mRNA transcription in corneal grafts after topical 0.5% FTY720 increased (p<0.05, n=3), while interleukin-2 (IL-2) and interferon-γ (IFN-γ) mRNA expression in corneal grafts treated with 1% CsA decreased (p<0.01, p<0.05, respectively). These cytokine results were paralleled by similar immunohistochemical staining. Topical 0.5% FTY720 and 1% CsA treatment reduced the infiltration of CD4+ Tcells in the grafts.

CONCLUSIONS

Topical 0.5% FTY720 and 1% CsA can effectively prolong allogeneic corneal graft survival in mice. Treatment with topical 0.5% FTY720 increases the percentage of CD4+ T cells and the percentage of Treg cells in cervical lymph nodes. The 0.5% FTY720 increased TGF-β1 mRNA expression and decreases infiltration of CD4+ T cells in corneal grafts, while topical 1% CsA down-regulated the expression of IL-2 and IFN-γ.

Authors+Show Affiliations

Departments of Ophthalmology, Chinese PLA General Hospital, Beijing, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22509094

Citation

Liu, Yong, et al. "Topical Application of FTY720 and Cyclosporin a Prolong Corneal Graft Survival in Mice." Molecular Vision, vol. 18, 2012, pp. 624-33.
Liu Y, Jiang J, Xiao H, et al. Topical application of FTY720 and cyclosporin A prolong corneal graft survival in mice. Mol Vis. 2012;18:624-33.
Liu, Y., Jiang, J., Xiao, H., Wang, X., Li, Y., Gong, Y., ... Huang, Y. (2012). Topical application of FTY720 and cyclosporin A prolong corneal graft survival in mice. Molecular Vision, 18, pp. 624-33.
Liu Y, et al. Topical Application of FTY720 and Cyclosporin a Prolong Corneal Graft Survival in Mice. Mol Vis. 2012;18:624-33. PubMed PMID: 22509094.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Topical application of FTY720 and cyclosporin A prolong corneal graft survival in mice. AU - Liu,Yong, AU - Jiang,Jingjing, AU - Xiao,He, AU - Wang,Xiaokui, AU - Li,Yan, AU - Gong,Yubo, AU - Wang,Dajiang, AU - Huang,Yifei, Y1 - 2012/03/09/ PY - 2011/10/07/received PY - 2012/03/06/accepted PY - 2012/4/18/entrez PY - 2012/4/18/pubmed PY - 2012/7/10/medline SP - 624 EP - 33 JF - Molecular vision JO - Mol. Vis. VL - 18 N2 - PURPOSE: To investigate the effects of topical FTY720 and cyclosporin A (CsA) on allogeneic corneal transplantation in mice. METHODS: A total of 75 BALB/c mice received corneal grafts from C57BL/6 donors. Recipients were treated with 0.1%, 0.3%, or 0.5% FTY720 ophthalmic gel or 1% CsA eye-drops after the graft (controls received no treatment). The number of cluster of differentiation (CD)4+ T cells and CD4+CD25+forkhead box P3 (Foxp3)+ regulatory (Treg) cell phenotypes were measured by flow cytometry. Cytokine mRNA expression in corneal grafts was analyzed by real-time quantitative PCR. CD4 + T cells and cytokines in corneal samples were identified by immunohistochemical staining. RESULTS: Corneal graft survival was prolonged by treatment with topical 0.5% FTY720 (mean survival time [MST], 24.1±1.6 days) or 1% CsA eye-drops (MST 25.0±1.9 days) compared with controls (MST, 13.4±0.5 days; n=9, both p<0.01). Topical 0.5% FTY720 treatment significantly increased the percentages of CD4 + T (p<0.05) and Treg cells (p<0.01; n=5) in the cervical lymph nodes compared with controls. Transforming growth factor-β1 (TGF-β1) mRNA transcription in corneal grafts after topical 0.5% FTY720 increased (p<0.05, n=3), while interleukin-2 (IL-2) and interferon-γ (IFN-γ) mRNA expression in corneal grafts treated with 1% CsA decreased (p<0.01, p<0.05, respectively). These cytokine results were paralleled by similar immunohistochemical staining. Topical 0.5% FTY720 and 1% CsA treatment reduced the infiltration of CD4+ Tcells in the grafts. CONCLUSIONS: Topical 0.5% FTY720 and 1% CsA can effectively prolong allogeneic corneal graft survival in mice. Treatment with topical 0.5% FTY720 increases the percentage of CD4+ T cells and the percentage of Treg cells in cervical lymph nodes. The 0.5% FTY720 increased TGF-β1 mRNA expression and decreases infiltration of CD4+ T cells in corneal grafts, while topical 1% CsA down-regulated the expression of IL-2 and IFN-γ. SN - 1090-0535 UR - https://www.unboundmedicine.com/medline/citation/22509094/Topical_application_of_FTY720_and_cyclosporin_A_prolong_corneal_graft_survival_in_mice_ L2 - https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22509094/ DB - PRIME DP - Unbound Medicine ER -