[HTML][HTML] Topical application of FTY720 and cyclosporin A prolong corneal graft survival in mice

Y Liu, J Jiang, H Xiao, X Wang, Y Li, Y Gong… - Molecular …, 2012 - ncbi.nlm.nih.gov
Y Liu, J Jiang, H Xiao, X Wang, Y Li, Y Gong, D Wang, Y Huang
Molecular vision, 2012ncbi.nlm.nih.gov
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 …
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.
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