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Takenori Inomata, Jing Hua, Tina Shiang, Homer Chiang, Reza Dana; Is Dry Eye Disease in Donors a Risk Factor for Corneal Graft Rejection?. Invest. Ophthalmol. Vis. Sci. 2016;57(12):1438.
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© 2017 Association for Research in Vision and Ophthalmology.
To assess the effect of dry eye disease (DED) in donors on allosensitization and graft rejection.
We induced DED in C57BL/6 mice. DED or healthy corneas were then transplanted onto BALB/c recipient mice. Graft survival and opacity scores were evaluated by slit lamp biomicroscopy (n=10 mice/group). Corneas and draining lymph nodes (dLNs) were harvested at day 14 post-transplantation (n=5 mice/group). We analyzed the frequencies of MHCIIhiCD11c+ mature dendritic cells (DCs) in the donor corneas and host dLNs using flow cytometry. IFN-γ- and IL-17-producing CD4 T cell frequencies and Foxp3 expression in Tregs in the dLNs were analyzed by flow cytometry. The enzyme-linked immunospot (ELISPOT) assay was used to assess T cell allosensitization via direct and indirect pathways (n=3/group).
Transplant recipients with DED donor corneas showed significantly reduced graft survival (10%) compared to control mice (50% survival, p=0.022). Recipients with DED donor corneas had significantly increased mature DCs in the grafted cornea (Healthy donor 35.4%±0.5 vs. DED donor 44.0%±0.36%; p<0.0001) and host dLNs (Healthy donor 13.7%±1.6 vs. DED donor 25.1%±0.66%; p=0.0051). Frequencies of IFN-γ- and IL-17-producing T cells were increased in the dLNs of recipients with DED corneas, while the expression (mean fluorescence intensity) of Foxp3 in Tregs was decreased (Healthy donor 6806±81 vs. DED donor 6004±193; p=0.0002). In addition, the direct pathway of allosensitization was significantly amplified in recipients with DED donor tissues per ELISPOT analysis (p=0.0146).
Our results suggest that DED in donors could be a significant risk factor for subsequent corneal graft rejection.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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