The ResolvinE1 Inhibits Corneal Allograft Rejection In High-risk Corneal Transplantation

Objective:To investigate the effects of Resolvin E1(RvE1)on corneal allograft rejection in a high –risk corneal allograft transplantation model.Methods:High-risk corneal beds were created via placement of intrastromal sutures in the corneas of BALB/c mice for 2 weeks.Allogeneic corneal transplantation was performed by transplanting corneas of C57BL/6 mice onto BALB/c hosts.RvE1 or normal saline(control)was subconjunctivally injected.Allograft survival was observed by slit lamp biomicroscope,and inflammatory cell infiltration was detected by HE and IHC.The percentage of Th1,Th17 and Treg cells in draining lymph nodes(DLNs)were evaluated by flow cytometric analysis.The levels of Th1,Th2,and Th17-associated cytokines in the grafts were measured by Cytometric Bead Array and Real-Time PCR.Results:RvE1 treatment significantly improved allograft survival compared to the control group.RvE1 treatment decreased the edema and the infiltration of neutrophils and CD4+ T(Th1/ Th17)cells in corneal grafts,and reduced the percentage of Th1/ Th17 cells in DLNs.In addition,RvE1 treatment significantly reduced the mRNA expression of pro-inflammatory cytokines including IL-1?,IL-1?,TNF-?,IL-2,IL-6,IFN-?,IL-17 A,IL-17 F,IL-21,and IL-22 in the graft.RvE1 treatment significantly reduced of protein levels of the pro-inflammatory cytokines,IL-2,TNF,IL-6,IFN-?,and IL-17.However,RvE1 treatment did not alter the percentage of Treg cells in DLNs and the expression of IL-4,IL-5,and IL-10.Conclusion:RvE1 treatment improves allogeneic corneal graft survival in a high-risk corneal transplantation model via inhibiting the Th1/Th17-related inflammation.RvE1 treatment did not alter Treg-related immune privilege.