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The study of the role of cell populations in rejection and tolerance of orthotopic corneal transplants
Sedláková, Klára ; Filipec, Martin (advisor) ; Jirásková, Naďa (referee) ; Čejková, Jitka (referee)
Small animal models of orthotopic corneal transplantation offer many advantages for the study of immune mechanisms after grafting - not only because of the similar mechanisms of murine and human corneal transplant rejection but also due to the feasibility of the direct observation of the animal without the need to sacrifice it. The purpose of the thesis was to study this model in mouse and rat. We established allotransplantation (BALB/c to C57BL/6 mouse and Wistar Furth to Lewis rat) and concordant xenotransplantation model (rat to mouse; Lewis to BALB/c and Sprague Dawley to BALB/c) and set up grading schemes for the evaluation of the clinical course after grafting. Initially, we focused on the effect of the suturing technique on the survival of xenografts and on the efficacy of selected immunosuppressants: cyclosporine A, monoclonal antibody against T cells (anti-Thy-1.2) and AMT (a specific inhibitor of inducible nitric oxide synthase, 2- amino-5.6-dihydro-6-methyl-4-H-1.3-thiazine)). The results demonstrate that the suturing technique significantly affects the outcome of transplantation and, importantly, influences the effectiveness of immunosuppressive regimens and therefore must be taken into account when evaluating the efficacy of immunosuppressive drugs. FTY720 is a novel immunosuppressant with a...

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