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

Abstract

SUMMARYThe modes of action of topical cyclosporin A were studied in rabbits. Immunorejection of corneal allografts was provoked by placing the grafts eccentrically, in contact with the limbus. Topical application of cyclosporin A five times daily for 28 days prevented the rejection of corneal allografts. All grafts were rejected in the control animals. The seven rabbits of the cyclosporin A group were subsequently treated for six months with a lower dosage of cyclosporin A 1%. In six rabbits the graft remained clear. One rabbit treated with two drops a day showed an allograft reaction that could be suppressed by increasing the dosage. After six months, discontinuation of the therapy resulted in rejection of all grafts within four weeks. Cyclosporin A could be detected in the plasma and aqueous humour of both eyes at the end of the treatment, raising the question whether the immunosuppressive effect of topically applied cyclosporin A was due to local or systemic action. Cyclosporin A 1% was therefore applied to the fellow eye five times daily following transplantation, and this treatment, producing similar plasma levels of cyclosporin A, failed to delay the rejection of eccentric corneal allografts. Consequently the suppression of the allograft rejection by topical cyclosporin A is primarily a local immunosuppressive effect, though systemic influence is not ruled out.

The Risk of Microbial Contamination in Multiple-Dose Preservative-Free Ophthalmic Preparations

“…20) Furthermore, ophthalmic preparations of 2% cyclosporine has been used for immune suppression after corneal transplantation. [21][22][23][24] For much-needed ophthalmic preparations, it is desirable to manage their use in accordance with their physicochemical properties. However, there is less evidence regarding the efficacy and safety of hospital preparations compared to commercially available ophthalmic preparations.…”

Effects of topical 2% cyclosporine A on the corneas of dogs subjected to lamellar keratoplasty with a graft of equine pericardium preserved in glycerin: clinical and morphological evaluation

“…Topical administration of cyclosporine A does not produce a measurable systemic concentration or contralateral ocular immunusupression (FOETS et al, 1985;BELIN et al, 1990;JACKSON et al, 1991;BENELLI et al, 1997;STEVENSON et al, 2000) enabling each animal to be its own control (JACKSON et al, 1991).…”

Efeito imunossupressor da ciclosporina intra-muscular administrada em diferentes períodos pós-operatórios em um modelo de transplante penetrante de córnea em ratos

“…Foets et al 7 obtiveram êxito em reverter episódios iniciais da rejeição aumentando a dose tópica da ciclosporina, enquando Roussel et al 22 observaram que os episódios iniciais somente poderiam ser atenuados mas não revertidos.…”

“…Pela sua ação inibidora na maturação dos linfócitos T, a ciclosporina tem sido utilizada nas fases iniciais do transplante, ou seja, antes de se realizar a cirurgia ou no pós-operatório imediato. Alguns autores obtiveram êxito em atenuar e até mesmo reverter episódios iniciais da rejeição com o uso da ciclosporina 7 , o que torna discutível qual o melhor momento para iniciar o tratamento com a droga a fim de se obter controle na rejeição do transplante de córnea 8 . Ainda é controverso se a ciclosporina é eficaz no controle de reações imunes em andamento o que significaria atuar durante a crise de rejeição 9 .…”