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Richard A. D. Mills, Douglas J. Coster, Keryn A. Williams; Effect of Immunosuppression on Outcome Measures in a Model of Rat Limbal Transplantation. Invest. Ophthalmol. Vis. Sci. 2002;43(3):647-655.
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purpose. To examine the effect of immunosuppression with intramuscularly
injected cyclosporine and topical corticosteroid on limbal allograft
survival in a new model in the inbred rat.
methods. Orthotopic limbal tissue harvested from male Fischer 344 (isografts) or
male Wistar-Firth donors (allografts) was sutured into superior and
inferior lamellar excision sites in female recipient Fischer 344 rats.
Grafts were examined clinically for at least 55 days. Superficial
epithelial cells were sampled weekly, and the DNA extracted and probed
for the male-specific gene Sry by polymerase
chain reaction. Recipients were killed at established intervals for
immunohistochemistry. Graft-recipient animals were randomly assigned to
receive either intramuscular cyclosporine plus topical prednisolone
phosphate or vehicle for 4 weeks from the time of transplantation.
results. Isografts survived for a median of more than 55 days.
Allografts underwent clinical rejection at a median of 6 to 7 days
after grafting. Acutely rejecting allografts showed a dense mononuclear
infiltrate consisting of activated CD4+ and
CD8+ T cells with some macrophages. Genomic Sry was usually detectable in cells sampled from the
ocular surface for more than 55 days in isografts, but not beyond 7
days in allografts. Immunosuppression prolonged allograft survival
significantly, as assessed clinically, but did not prolong donor cell
survival on the ocular surface, as assessed by detection of genomic Sry.
conclusions. A robust model of limbal transplantation was developed in the rat.
Isografts survived for the long term, whereas allografts underwent
rapid rejection. Although clinical allograft survival was prolonged to
a modest extent by immunosuppression, donor cell survival on the ocular
surface was not improved.
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