Corneal Tissue From Dry Eye Donors Leads to Enhanced Graft Rejection. Issue 1 (January 2018)

• Record Type: Journal Article
• Authors: Inomata, Takenori; Hua, Jing; Nakao, Takeshi; Shiang, Tina; Chiang, Homer; Amouzegar, Afsaneh; Dana, Reza
• Is Part Of: Cornea. Volume 37:Issue 1(2018)
• Publication Date: 2018-01
• Subjects: dry eye disease -- corneal transplantation -- graft rejection -- dendritic cell -- allosensitization; Cornea -- Periodicals; Cornea -- Periodicals; Cornée -- Périodiques; 617.719
• DOI: 10.1097/ICO.0000000000001400
• Languages: English
• ISSNs: 0277-3740

Abstract

Abstract : Purpose: To assess the effect of dry eye disease (DED) in graft donors on dendritic cell (DC) maturation, host T-cell sensitization, and corneal allograft rejection. Methods: Corneas of control (healthy donor) and DED mice (C57BL/6) were transplanted onto fully allogeneic naive BALB/c recipients (n = 10 mice/group). Long-term allograft survival was evaluated for 8 weeks. Corneas and draining lymph nodes (dLNs) were harvested at posttransplantation day 14 (n = 5 mice/group). The frequencies of MHCII high CD11c + DCs in the donor corneas and host dLNs and the frequencies of interferon (IFN)-γ + and IL-17 + CD4 + T cells and Foxp3 expression by Tregs in host dLNs were investigated using flow cytometry. The enzyme-linked immunospot assay was used to assess host T-cell allosensitization through direct and indirect pathways (n = 3/group). Results: Recipients of DED donor corneas showed significantly reduced graft survival (10%) compared with control mice (50% survival, P = 0.022), and had significantly increased frequencies of mature DCs in the grafted cornea (DED donor 44.0% ± 0.36% vs. healthy donor 35.4 ± 0.5%; P < 0.0001) and host dLNs (DED donor 25.1% ± 0.66% vs. healthy donor 13.7% ± 1.6%; P = 0.005). Frequencies of IFN-γ + and IL-17 + T cells were increased in the dLNs of recipients of DED corneas, whereas the expression (mean fluorescence intensity) of Foxp3 in Tregs was decreased significantly in these mice (DED donor 6004 ± 193 vs. healthy donor 6806 ± 81; P = 0.0002). Enzyme-linked immunospot analysis showed that the direct pathway of allosensitization was significantly amplified in recipients of grafts with DED ( P = 0.0146). Conclusions: Our results indicate that DED in the donor is a significant risk factor for subsequent corneal allograft rejection.