Resolvin E1 Inhibits Corneal Allograft Rejection in High-Risk Corneal Transplantation

PURPOSE. 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 hematoxylin and eosin and immunohistochemistry. 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. After RvE1 treatment, the infiltration of neutrophils and CD4(+) T (Th1/Th17) cells were decreased in corneal grafts, and the percentage of Th1/Th17 cells in DLNs were reduced. In addition, RvE1 treatment significantly reduced the mRNA expression of proinflammatory cytokines in the graft including IL-1 alpha, IL-1 beta, TNF-alpha, IL-2, IL-6, IFN-gamma, IL-17A, IL-17F, IL-21, and IL-22 as well as the protein level of the proinflammatory cytokines, including IL-2, TNF, IL-6, IFN-gamma, 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. CONCLUSIONS. RvE1 treatment improves allogeneic corneal graft survival in a high-risk corneal transplantation model via inhibiting the Th1/Th17-related inflammation.