Cyclosporine玻璃体腔内注射对异种视网膜色素上皮移植的排异抑制作用

Inhibitory effects of Cyclosporine intravitreal injection to retinal pigment epithelium xenografts in sub-retinal spaces

目的 观察兔眼视网膜下腔植入人胚眼视网膜色素上皮 (retinal pigm ent epithe-lium,RPE)后不同时期的眼底和组织学改变。研究环胞菌素 A (Cyclosporines,Cs A )玻璃体腔内注射能否抑制人胚眼 RPE在兔眼视网膜下腔中诱导的异种移植排异反应。方法 人胚眼色素上皮片和浓缩色素上皮细胞悬液植入 36只兔眼的视网膜下腔 ,其中 16眼为对照组 ,用于观察排异的自然转规。分别于 7d(8眼 )和 30 d(8眼 )后获取组织标本。另 2 0眼为实验组。RPE移植后 ,每周一次玻璃体腔内注射 Cs A1mg(12眼 )或 Cs A0 .1mg(8眼 )。视网膜和视神经的毒性反应使用 ERG进行检查。结果 人胚眼 RPE片和浓缩的 RPE细胞均能在视网膜下腔短期存活。移植的 RPE与视细胞结合良好并显示吞噬功能。排异反应发生时间约在术后 10～ 30 d。对照组中 7d的排异发生率为 0 /8;30 d排异发生率为 7/8。排异发生后荧光造影中移植区为高荧光区 ,组织切片中显示有大量的组织细胞积聚。 Cs A1mg组 30 d排异发生率为 0 /12 ,0 .1mg组为 5 /8。ERG波幅的下降与 Cs A剂量和注射次数呈正相关。结论 异种 RPE视网膜下腔移植在无免疫抑制剂的条件下 ,只能短期存活。Cs A玻璃体腔中注射能抑制异种 RPE移植的排异反应但易引起明显的视网膜毒性反应。

Objective To observe fundus, angiographic and histological changes of rabbit eyes in which human fetal RPE cells were transplanted into subretinal spaces. To determine if intravitreal injection of Cyclosporine (CsA) can prevent the rejection of human fetal RPE xenografts to rabbit retina. Methods RPE patches and concentrated RPE cell suspension from human fetal eyes were transplanted into subretinal spaces of 36 rabbit eyes. In control group, the eyes were removed for histological examination at 7d (8 eyes) and 30d (8 eyes). Some rabbits (4 eyes) were received vehicle injection for comparison. The remaining twenty eyes received weekly intravitreal CsA 1mg (12 eyes) or 0.1mg (8 eyes) injection. The ERG was recorded to check retinal toxicity of CsA and vehicle. Results Both RPE patches and concentrated RPE cell suspension from human fetal eyes can survive in subretinal spaces of rabbit eyes. Transplanted RPE kept good contact with visual cells and phagocytized outer disks. In control group, rejection rate was 0/8 in one week and 7/8 in four weeks. The transplanted area was hyperfluorescent in angiography and also heavily infiltrated by large amounts of histocytes. In CsA treated group, the rejection rate at one month was 0/12 with 1 mg of CsA and 5/8 for 0.1mg injection. The ERG showed a CsA dose and time dependent reduction. Conclusion The survival time of human fetal RPE xenografts is very limited in the subretinal spaces if immunosuppressive agents aren't administered. Intravitreal CsA delays rejection of RPE xenografts in rabbits but causes marked retinal toxicity.