Corneal graft rejection: a new rabbit model and cyclosporin-A.

Abstract

In order to test the efficacy of topically applied cyclosporin-A in preventing corneal allograft rejection, existing rabbit models were modified to produce a new model in which the allograft reaction could be consistently initiated solely as a result of corneal transfer without any additional means of sensitisation. With this model, which reflects clinical corneal grafting more closely than many previous models, cyclosporin-A 1% drops applied to the recipient eye 5 times daily for 4 weeks inhibited corneal graft rejection. When cyclosporin-A 1% drops were applied to corneal allografts for 13 weeks, 44% of grafts remained clear 180 days after transplantation. No side effects were observed that could be attributed to topically applied cyclosporin-A.

Prolonged survival of allogeneic corneal grafts in rabbits treated with topically applied cyclosporin A: systemic absorption and local immunosuppressive effect.

“…The results of experiment 1 "' confirm earlier reports5 6 that cyclosporin A 1% in oil eye drops applied to the recipient eye inhibit the rejection of corneal allografts in rabbits. A single retrobulbar injection of cyclosporin A" in oil likewise prolongs corneal allograft survival in rabbits.…”

“…This is contrary to Hunter and colleagues' findings that 44% of the grafts treated for three months with cyclosporin A 1% eye drops remained clear after the end of the treatment. 6 The most likely explanation of this difference is that we placed the allografts more closely to the limbus. In Hunter and colleagues'6 experiment reactivation of the corneal blood vessels also resulted in typical corneal rejecti'on in spite of the previous treatment with cyclosporin A.…”

Efficacy of subconjunctival cyclosporin-containing microspheres on keratoplasty rejection in the rabbit

“…Various vegetable oils [9,15], petrolatum [24], cremophor [18] and azone [25] have been tested as vehicles, but it is difficult to attain high levels of the drug over a prolonged period.…”

Inflammation of the external eye

“…Cyclosporine, which may affect interleukin 1, interleukin 2, and the inducer T cell, has not been employed for external ocular inflammation, despite reports on its effectiveness in suppressing corneal graft rejection in rabbits [Hunter et al, 1982;Bell et al, 1982).…”