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J. Schwartzkopff, D. R. Saban, A. Beiter, I. T. Gross, F. Birnbaum, D. Böhringer, T. Reinhard; Corneal Antigen Presenting Cells Promote Allograft Survival. Invest. Ophthalmol. Vis. Sci. 2009;50(13):1964.
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The risk of corneal allograft rejection seen clinically in children and in infants is considerably high. Baby rat recipients have previously been described as a good model to study this, as they indeed demonstrate accelerated rejection. In this set of experiments a potential difference in the immunogenicity of a corneal transplant depending on the donor age was analyzed in the baby rat model.
Corneal allografts were harvested from baby or adult Fisher rats (3 or 10 weeks old respectively) and orthotopically placed on Lewis rats. 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 antigen presenting (APC) cells were performed by fluorescence and confocal microscopy.
In contrast to normal adult corneas, the center of normal baby corneas from donor Fisher rats had large numbers of APCs (DC, CD11c, MHC-II, CD163) 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 (p<0.01). 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.
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 born by baby corneal epithelium. We therefore demonstrate evidence that donor corneal APC can promote corneal graft survival.
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