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Hui Zhang, Stephanie Chen, Lu Chen; Corneal Lymphangiogenesis is Highly Associated with Transplant Rejection in Different Mouse Strains. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1149.
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Mouse genetic background significantly affects the outcomes of corneal transplantation. This study is to investigate whether corneal transplantation-induced hemangiogenesis (HG), lymphangiogenesis (LG), or both are associated with the graft survival in different mouse strains.
Three sets of orthotopic corneal transplantations were performed in normal adult BALB/c and C57BL/6 mice: 1) BALB/c (donor) to BALB/c (recipient); 2) C57BL/6 (donor) to BALB/c (recipient); and 3) BALB/c (donor) to C57BL/6 (recipient). Corneal grafts wereobserved by ophthalmic slit-lamp biomicroscopy for 6 weeks and the survival was assessed by Kaplan-Meier analysis. Additionally, whole-mount flat corneas were also sampled by the end of the study for immunofluorescent microscopic assays using specific antibodies against CD31 (a panendothelial cell marker) and LYVE-1 (a lymphatic marker). The difference of corneal HG and LG among three transplantation settings and their correlation with transplant outcomes were analyzed.
Significant correlation was identified between corneal LG and transplant rejection. While the highest degree of LG was observed in allografts of the lowest survival rate (BALB/c donors to C57BL/6 recipients), only moderate LG was detected in the allografts with higher survival rate (C57BL/6 donors to BALB/c recipients). Additionally, minimal LG was detected in the syngeneic grafts which enjoy 100% survival. Such phenomenon was not observed for blood vessels.
Corneal transplantation-induced LG differs significantly among genetic backgrounds and is a major factor determining transplant rejection. Further studies on this new phenomenon may shed some light on our understanding of corneal transplant immunity as well as the development of therapeutic strategies to treat transplant rejection.
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