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Corneal Epithelial Rejection in the Rat

¹ From the Department of Ophthalmology, Royal Victoria Infirmary, Newcastle-upon-Tyne, United Kingdom; and the ² Division of Ophthalmology, School of Medical Sciences, Bristol, United Kingdom.

PURPOSE. To investigate clinical and histologic changes in the epithelium during corneal graft rejection in the rat.

METHODS. LEW (RT1^l) or PVG (RT1^c) strain corneas were transplanted to PVG strain recipients and examined by slit lamp for clinical signs of rejection. Recipients were killed, and corneal epithelial sheets were removed and examined by adenosine diphosphatase (ADPase) staining for Langerhans cells (LC) and by immunohistology for leukocytes and adhesion molecules (T cells, macrophages, granulocytes, major histocompatibility complex [MHC] class II, CD2 and CD54 intercellular adhesion molecule [ICAM]-1) at a range of time points before, during, and after rejection, depending on the cell type sought. Normal and contralateral eyes were examined for ADPase⁺ and MHC class II⁺ cells.

RESULTS. Clinical rejection, as defined by stromal opacity, occurred between days 10 and 15 after transplantation. In 94% of allografts, a curved clinical epithelial rejection line was observed in which ADPase⁺/MHC class II⁺, CD4⁺, or CD8⁺ T cells were identified. There were significantly more infiltrating cells of all types in epithelia of allografts than in those of isografts. The most numerous cells were CD4⁺ and CD8⁺ T cells, suggesting preferential migration of these cells into the epithelium from underlying layers. Expression of MHC class II and ICAM-1 was induced on epithelial cells.

CONCLUSIONS. Epithelial rejection in rats is clinically similar to that in humans and occurs simultaneously with stromal infiltration. It may be mediated by T cells rather than macrophages. In isolation, its recognition in humans may be a useful indication that the patient is at high risk of endothelial rejection.

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