Suppression of corneal graft rejection in rabbits by local administration of immunosuppressive agents.

角膜移植排斥反应是导致角膜移植手术失败的主要原因之一。器官移植成功率的显著提高是由于引入了一种新的、强效的免疫抑制剂环孢素。本研究旨在探讨局部应用新型免疫抑制剂对兔角膜移植排斥反应的抑制作用。(1)环孢素（CYA）以往研究报道的环孢素滴眼液为油溶液。与以往的报道相比，我们发现对角膜渗透能力最强的药物是含有α -环糊精（α - CD）的CYA。对10对家兔进行7mm交换穿透性角膜移植术。第一组10只眼给予0.025% CYA滴眼液。第二组10只眼只给予40 mg/ml α - CD滴眼液，两种滴眼液每天4次。移植100 d后，CYA治疗组10只眼均保持透明，对照组10只眼中有4只眼保持透明。在第二项研究中，7只不透明的兔移植物进行再移植，每天局部给予4次CYA。在第三项研究中，我们在出现移植排斥反应时使用CYA滴眼液进行治疗。7只眼睛中有5只处于早期排斥期，另外2只处于晚期排斥期。早期5只眼均停止排斥反应并保持清澈，但晚期2只眼因血管形成而浑浊。(2) FK - 506对7只不透明兔进行再移植，每周1次给予0.1 mg/kg FK - 506结膜下注射。7只眼中有6只在移植100天后仍保持清晰。

Corneal graft rejection is one of the leading causes of failure in corneal graft surgery. A significant improvement in the success rate in organ transplantation was achieved by the introduction of a new, powerful immunosuppressant, ciclosporin. The purpose of our research is to find the effect on the suppression of corneal graft rejection in rabbit by local administration of new immunosuppressive agents.(1) Ciclosporin (CYA) The vehicles of CYA eye drops which had been reported in the past study were oil solutions. We found that the drug with the greatest penetrating ability into the cornea was CYA with alph - cyclodextrin (alpha - CD), compared with the previous reports. 7mm exchange penetrating keratoplasties were performed on 10 pairs of rabbits. Group I consisting of 10 eyes was given 0.025% CYA eye drops. Group II consisting of 10 eyes was given only 40 mg/ml of alpha - CD. Both eye drops were given 4 times daily. 100 days after grafting, all 10 eyes in CYA treated groups remained clear and 4 eyes out of 10 in control group remained clear. In second study, 7 opaque grafts of rabbits were performed regraft and were given CYA topically 4 times daily. In third study, we treated with CYA eye drops at the onset of graft rejection. Five eyes out of 7 were at early stage of rejection and other two eyes were at late stage. All five eyes at early stage stopped rejection and remained clear, but two eyes at late stage became cloudy with vascularization.(2) FK - 506 Seven opaque grafts of rabbits were performed regraft and were given 0.1 mg/kg FK - 506 subconjunctival injection once a week. 6 eyes out of 7 remained clear 100 days after re - grafting.