Abstract

P 152

Corneal antigen presenting cells contribute to allograft survival in the baby rat

Johannes Schwartzkopff1, Daniel Saban2, Anna Beiter1, Isabel Gross1, Florian Birnbaum1, Daniel Böhringer1, Thomas Reinhard1
1Universitäts-Augenklinik Freiburg, 2Schepens Eye Research Institute, Harvard Medical School, Boston, MA, USA

Objective
The risk of corneal allograft rejection seen in infants younger than 3 years of age is considerably high. We could show, that baby rats indeed demonstrate accelerated rejection. In this set of experiments the immunogenicity of a corneal transplant depending on the donor age was analyzed in the baby rat model.
Methods
Group 1: Corneal allografts were harvested from 3-week-old (baby) or 10-week-old (adult) Fisher rats and orthotopically placed on baby Lewis recipients. Group 2: Furthermore, grafts were depleted of antigen presenting cells (APC) prior to keratoplasty by UVB-irradiation and transplanted. Group 3: In addition chimeric corneal allografts consisting of stroma-endothelium from adult Fisher rats covered by corneal epithelium from baby Lewis rats (or reciprocal chimeric grafts) were also placed orthotopically on baby Lewis rats. Graft opacity was regularly assessed until rejection and immunohistological analyses of corneal APC (MHC-II+, CD11c+, CD163+) were performed by confocal microscopy.
Results
In contrast to normal adult corneas, the center of normal baby corneas from donor Fisher rats showed large numbers of APC in the epithelial layer. Nonetheless, rejection of such baby allografts was markedly decreased in baby recipients (p< 0.01), and similarly observed in adult recipients as well (group 1) (p< 0.01). Depletion of corneal APC reversed the immunological exeptional position of a young graft and lead to significant rejection rate in group 2 that was comparable to the one obeserved for old corneal allografts. Interestingly, chimeric allografts bearing baby corneal epithelium covering adult stroma-endothelium, showed a strong decrease in the rejection rate (p< 0.01) compared to reciprocal chimeric allografts (group 3).
Conclusions
The immunogenicity of baby corneal allografts appears to be markedly reduced relative to adult donors. Furthermore, our data suggest that this is due to donor corneal APC in the baby corneal epithelium. We therefore demonstrate evidence that donor corneal APC can promote corneal graft survival.

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