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Maryam Tahvildari, Parisa Emami-naeini, Masahiro Omoto, Daniel Saban, Sunil Chauhan, Reza Dana; Pretreatment of Donor Corneas with Anti-Inflammatory Cytokines Promotes Allograft Survival in High-Risk Corneal Transplantation. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4025.
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© ARVO (1962-2015); The Authors (2016-present)
Antigen presenting cells (APC) in the donor cornea are crucial to host sensitization and graft rejection. Given that in vitro manipulation of APCs may induce tolerogenic function to these cells, we evaluated whether treatment of donor corneas with IL-10 and TGF-β prior to transplantation could increase survival of high-risk corneal transplants by inducing tolerogenic APCs in the graft.
Corneal transplantation was performed using BALB/c (H-2d) mice as recipients and C57BL/6 (H-2b) mice as donors. Corneal sutures were placed on host corneas two weeks before transplantation to induce inflamed high-risk graft beds. Forty-eight hours before transplantation, donor eyes received a single subconjunctival injection of IL-10 and TGF-β (6 ng/µl in 10 µl saline) or saline alone (as a control). Phenotypic characteristics of graft APCs were determined at the time of transplantation using flow cytometry. Allografts were examined weekly to determine graft opacity scores using a standard grading system (from 0 to 5) and a Kaplan Meier analysis was used to calculate graft survival up to eight weeks after transplantation.
Treatment of donor corneas with IL-10 and TGF-β induced tolerogenic APCs in the grafts, as reflected by reduced frequencies of MHCII+CD11c+ cells (5.29% vs. 13.34% in control group, p=0.032) and CD40+CD11c+ cells (1.67% vs. 10.52% in control group, p=0.02). Weekly examination of the grafts showed decreased opacity scores in the cytokine treated group compared to controls from three to eight weeks after transplantation. This difference became most prominent at eight weeks post-transplantation with a mean opacity score of 1.65 compared to 2.7 in the control group, p=0.008. Analysis of graft survival showed a significant increase in the cytokine treated group (68.75%, n=16) compared to saline treated controls (20%, n=20, p=0.033) up to eight weeks after transplantation.
Pretreatment of donor corneas with IL-10 and TGF-β significantly increased long-term corneal allograft survival suggesting that this can be a promising strategy to improve graft outcomes in patients at high risk for graft rejection.
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