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Graft Rejection in a Rat Keratoplasty Model with Adult and Immature Recipients

1Mayer K., 1Reinhard T., 1Reis A., 2Claas F. J. H., 1Sundmacher R.,
1Heinrich-Heine-Universität Düsseldorf, Universitäts-Augenklinik (Düsseldorf)
2Leiden University Medical Center, Departement of Immunohematology and, Blood Transfusion (Leiden)

Purpose: Penetrating keratoplasty in infants still has a poor prognosis compared to keratoplasty in adults. This might be due to an elevated risk for graft rejection. Aim of this study was to compare rejected grafts of adult and three week old immature recipients in the rat keratoplasty model on an immunohistological basis.
Method: Forty orthotopic penetrating keratoplasties were performed in four groups. Group 1: adult Lewis recipients and donors; group 2: immature Lewis recipients and adult Lewis donors; group 3: adult Lewis recipients and adult Fisher donors; group 4: immature Lewis recipients and adult Fisher donors. For immunohistological evaluation all recipients were sacrificed on day fourteen. Immunohistology was performed using monoclonal mouse anti-rat antibodies against CD4, CD8 and OX62 (dendritic cells).
Results: Both allogeneic groups (group 3 and 4) showed a dense infiltration with CD4+ and CD8+ cells. The density of infiltrating CD4+ cells in the graft stroma, however, was nearly twice as high in the adult group (group 3) as compared to the immature group (group 4) (p<0.01). The density of infiltrating CD8+ cells in the graft stroma was more than fifty percent higher in the adult allogeneic group (group 3) than in the immature allogeneic group (group 4) (p<0.01). Both allogeneic groups were moderately infiltrated with OX62+ cells.
Conclusions: We were able to establish for the first time an animal model for keratoplasty in infants. First results in this rat keratoplasty model show a weaker T-cell response to corneal graft antigen in three week old rats. At the moment it is not yet obvious if this observation may explain the worse graft prognosis in infants.