Cyclosporine a drug-delivery system for high-risk penetrating keratoplasty: Stabilizing the intraocular immune microenvironment.
Cyclosporine a drug-delivery system for high-risk penetrating keratoplasty: Stabilizing the intraocular immune microenvironment.
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环孢素是一种用于高风险穿透性角膜移植术的药物输送系统：稳定眼内免疫微环境
DOI：
10.1371/journal.pone.0196571
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Shi W
中科院分区：
文献类型：
--
作者：
Zhang T;Li Z;Liu T;Li S;Gao H;Wei C;Shi W
环孢霉素A（CsA）是用于预防角膜移植排斥反应的重要药物。我们的初步研究表明，CsA药物传递系统（DDS）在预防高危角膜移植排斥反应方面比局部应用CsA更有效。然而，CsA DDS对眼内免疫微环境的影响尚未完全阐明。在本研究中，我们使用高危穿透性角膜移植术的兔模型，研究CsA DDS对角膜移植物、房水和虹膜睫状体的影响。新西兰白色兔随机分为正常对照组、未治疗组、CsA滴眼液组和CsA DDS组。术后3周和12周观察移植物存活情况，并评价CsA DDS的疗效。在CsA DDS组，平均移植物存活时间显着延长时，与未处理组和CsA滴眼液组相比。在所有时间点，CsA DDS组的朗格汉斯细胞密度、炎性细胞密度和中央角膜厚度均明显低于未治疗组和CsA滴眼液组（均P < 0.01），而未治疗组和CsA滴眼液组的朗格汉斯细胞密度、炎性细胞密度和中央角膜厚度均明显高于正常对照组（均P < 0.01）。与未治疗组和CsA滴眼液组相比，CsA DDS植入组角膜移植片中的CD 11b+和CD 8 + T细胞浸润明显减少。CsA DDS治疗还显著降低了角膜移植物和虹膜睫状体中的CD 4 + T细胞密度和干扰素-γ、白细胞介素-2（IL-2）、IL-6、CD 80和CD 86 mRNA的表达（均p < 0.01）。CsA DDS还能显著降低房水中IL-2水平（P < 0.01）。综上所述，我们的研究结果表明，CsA DDS植入前房创建一个相对的免疫抑制微环境中的角膜移植，虹膜睫状体，和房水。稳定眼内免疫微环境可部分阐明CsA DDS抑制角膜移植排斥反应的机制。
Cyclosporine A (CsA) is an essential medication used to prevent corneal allograft rejection. Our preliminary studies revealed that CsA drug-delivery system (DDS) was more effective in preventing high-risk corneal allograft rejection than topical CsA application. However, the impacts of CsA DDS on the intraocular immune microenvironment were not fully elucidated. In the present study, we investigated the effect of CsA DDS on the cornea allograft, aqueous humor, and iris-ciliary body using a rabbit model of high-risk penetrating keratoplasty. New Zealand white rabbits were divided into four groups: a normal control group, an untreated group, a CsA eye drop group and a CsA DDS group. Graft survival was monitored for 12 weeks, and the therapeutic effects of CsA DDS were evaluated at 3 and 12 weeks after high-risk keratoplasty. In the CsA DDS group, the mean graft survival time was significantly prolonged when compared with the untreated and CsA eye drop groups. At all time-points, Langerhans cell density, inflammatory cell density, and central corneal thickness in the CsA DDS group were much lower(all p < 0.01) than the untreated and CsA eye drop groups, in which their parameters were significantly higher than the normal control group (all p < 0.01). Compared with the untreated and CsA eye drop groups, an implanted CsA DDS markedly decreased the CD11b+ and CD8+ T cell infiltration in the corneal grafts. CsA DDS treatment also greatly reduced the CD4+ T cell density and the expression of interferon-gamma, interleukin-2 (IL-2), IL-6, CD80, and CD86 mRNA both in the corneal graft and iris-ciliary body (all p < 0.01). Moreover, CsA DDS significantly reduced the IL-2 level in aqueous humor (p < 0.01). Taken together, our results suggest that CsA DDS implanted into the anterior chamber create a relative immunosuppressive microenvironment in the corneal graft, iris-ciliary body, and aqueous humor. Stabilizing the intraocular immune microenvironment could partially elucidate the mechanism of CsA DDS in suppressing corneal graft rejection.
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DOI：
10.4049/jimmunol.1601135
发表时间：
2016-09-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Adams AB;Ford ML;Larsen CP
通讯作者：
Larsen CP
影响因子：
3.4
作者：
Nicholls, Susan M.;Banerjee, Sanjiv;Dick, Andrew D.
通讯作者：
Dick, Andrew D.
T淋巴细胞和同种异体移植排斥的同种异体认识。
影响因子：
7.3
作者：
Marino J;Paster J;Benichou G
通讯作者：
Benichou G
影响因子：
1.7
作者：
Qazi Y;Hamrah P
通讯作者：
Hamrah P
影响因子：
8.1
作者：
Lass, Jonathan H.;Benetz, Beth Ann;Beck, Roy W.
通讯作者：
Beck, Roy W.