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Johannes Schwartzkopff, Leslie Y. Olivares Valdez, Laura Bredow, Armin Buchwald, Daniel Böhringer, Thomas Reinhard; Sanglifehrin A Promotes Allograft Survival in Rat Keratoplasty. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1159.
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Immunosuppressive strategies e.g. Cyclosporine A (CsA) promote corneal graft survival by inhibiting T cells. As soon as treatment is stopped, rejection occurs mainly because T cells are still activated by dendritic cells (DC). It is of major interest to develop strategies to selectively block DC before the initial sensitization process comes up. Therefore, the selective blockade of DC by Sanfglifehrin A (SFA) was analyzed.
Penetrating keratoplasty was performed between Lewis recipient and Fisher donor rats. Recipients were injected with SFA, empty vehicle, or SFA in combination with a low dose of CsA intraperitoneally for two weeks, respectively. Controls received either low or high-dose CsA alone. Transplants were monitored for clinical signs of rejection. Serum levels of SFA and CsA were analyzed by mass spectrometry. Finally, histological evaluations for mononuclear infiltrates were performed on the day of rejection.
Intraperitoneal injection of SFA or CsA resulted in a dose dependent, stable serum level, respectively. No statistically significant effect was observed on graft survival by injecting empty vehicle or low-dose CsA. High dose CsA ameliorated median graft survival time significantly (p<0.01), however all transplants were rejected after treatment was stopped. SFA treatment resulted in long-term survival of more than 60% of corneal grafts (p<0.01). Infiltration of mononuclear cells was significantly reduced in animals receiving SFA compared to all other groups.
Blockade of the priming process by affecting DC using SFA has a long term effect on graft survival in rat keratoplasty. Therefore, SFA seems a promising immunosuppressive drug to prevent the initiation of rejection episodes following keratoplasty.
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