Suppression of corneal graft rejection by subconjunctival injection of FK-506 in a rat model of penetrating keratoplasty.

The usefulness of the subconjunctival injection of FK-506 for suppression of allograft rejection was investigated in a rat model of orthotopic penetrating keratoplasty. Fischer rats were used as donors and Dark Agouti rats, as recipients. FK-506 was administered subconjunctivally in a dosage of 0.3 mg/kg/day for 15 consecutive days after penetrating keratoplasty was performed. Allograft rejection occurred within 8 to 10 days after keratoplasty in all untreated rats (n = 6). None of the FK-506-treated rats (n = 6) exhibited graft rejection during the 3-week observation period. Histologic examination showed marked infiltration of mononuclear cells in the stroma of corneal grafts from untreated rats 3 weeks after grafting. Inflammatory cells were only occasionally observed in grafts from FK-506-treated rats. Donor-specific cytotoxic T lymphocyte activity was completely suppressed in FK-506-treated rats 3 weeks after grafting. Our results indicated that subconjunctival injection of FK-506 effectively prevented corneal allograft rejection in a rat model of penetrating keratoplasty.