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

局部给予免疫抑制剂抑制兔角膜移植排斥反应。

• 批准号: 63570839
• 负责人: KANAI Atsushi
• 金额: $ 1.34万
• 依托单位: Juntendo University, Dept. of Ophthalmology
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1988
• 资助国家: 日本
• 起止时间: 1988 至 1989
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-63570839/
• 关键词: graft rejection; rabbit cornea; transplantation; ciclosporin; FK-506; re-graft; 家兎眼同種角膜移植; 家兎眼異種角膜移植; α-シクロデキストリン; αーシクロデキストリン; 角膜内移行; 家兎角膜移植

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.

角膜移植排斥反应是角膜移植手术失败的主要原因之一。由于采用了一种新的强效免疫抑制剂环孢素，器官移植的成功率有了显著提高。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）在过去的研究中报道的CYA滴眼液的载体是油溶液。与以往报道相比，我们发现CYA与α-环糊精（α- CD）的角膜渗透能力最强。对10对家兔施行7 mm穿透性角膜移植术。第1组10眼，滴用0.025%CYA滴眼液。第二组10只眼，仅给予40 mg/ml的α- CD.两种滴眼液每天给药4次。术后100天，CYA治疗组10只眼均保持透明，对照组10只眼中4只保持透明。第二组7只兔移植物不透明，行再次移植，每天4次给予CYA局部给药。在第三项研究中，我们在移植排斥反应发生时使用CYA滴眼液进行治疗。排斥反应早期5眼，晚期2眼。早期5只眼均停止排斥反应，保持透明，但晚期2只眼因血管形成而混浊。(2)FK - 506将7只家兔的不透明移植物进行再移植，每周一次结膜下注射FK - 506 0.1mg/kg。7只眼中6只眼术后100天仍保持透明。

项目成果

Kanai, A. et al: "Effect of ciclosporin eye drops on the survival of corneal grafts in rabbit." XII Asia-Pacific Acad Ophthalmol Proceedings 1990.

Kanai, A. 等人：“环孢素滴眼液对兔子角膜移植物存活的影响。”

Alba,R.M.;Kanai,A.;Takano,T.;Kobayashi,C.;Nakajima,A.;Kurihara,K.;Fukami,M.: 日本眼科紀要. 40. (1989)

Alba，R.M.；Takano，T.；Nakajima，A.；Fukami，M.：日本眼科杂志 40。

Kobayashi C.et al.: "Suppression of corneal graft rejection in rabbit by a new immunosuppressive agent,FK-506" Transplantation Proceedings. 21. 3156-3158 (1989)

Kobayashi C.等人：“新型免疫抑制剂 FK-506 抑制兔角膜移植排斥反应”移植论文集。

Alba, R.M. et al: "The effect on the cornea of various vehicles for cyclosporin eye drops." Folia Ophthal Jpn 40, 902-908, 1989.

阿尔巴，R.M.

Kanai, A. et al: "The effect on the cornea of alpha cyclodextrin vehicle for cyclosporin eye drops." Transplantation Proceedings, 21, 3150-3152, 1989.

Kanai, A. 等人：“环孢素滴眼液中 α 环糊精载体对角膜的影响。”