Lai C C, Gouras P, Doi K, Tsang S H, Goff S P, Ashton P
Department of Ophthalmology, Columbia University, Howard Hughes Medical Institute, New York, New York 10032, USA.
Invest Ophthalmol Vis Sci. 2000 Sep;41(10):3134-41.
To determine whether local immunosuppression with Cyclosporin A can influence the survival of human fetal retinal pigment epithelium (RPE) xenografts in the rabbit's subretinal space.
Cultured human fetal RPE cells were transduced with the gene for green fluorescent protein (GFP) using a lentiviral vector. The RPE was transplanted into the subretinal space of rabbits that received intravitreal cyclosporine either by weekly injections (0. 25-0.5 mg) or by slow release (approximately 2 microg/d) from a capsule sutured into the vitreal cavity after prior cryopexy. The transplanted RPE was followed by GFP fluorescence scanning laser ophthalmoscopy and by histology of the transplant site.
RPE xenografts in eyes receiving intravitreal cyclosporine survived longer (several months) than they did in control eyes without cyclosporine. Survival was as long with slow release capsules as it was with weekly intravitreal injections at much higher concentrations of cyclosporine.
Local immunosuppression of the eye with cyclosporine prolongs the survival of RPE xenografts in the subretinal space of rabbits, implying that rejection involves activated T lymphocytes. Local immunosuppression with slow release capsules is as effective as weekly injections at much higher concentrations.
确定用环孢素A进行局部免疫抑制是否会影响人胎儿视网膜色素上皮(RPE)异种移植物在兔视网膜下间隙的存活。
使用慢病毒载体将绿色荧光蛋白(GFP)基因转导至培养的人胎儿RPE细胞。将RPE移植到兔的视网膜下间隙,这些兔通过每周注射(0.25 - 0.5毫克)或在预先进行冷冻治疗后,通过缝合到玻璃体腔的胶囊缓慢释放(约2微克/天)接受玻璃体内环孢素。通过GFP荧光扫描激光眼科检查和移植部位的组织学检查对移植的RPE进行跟踪。
接受玻璃体内环孢素的眼中的RPE异种移植物比未接受环孢素的对照眼中的移植物存活时间更长(数月)。在环孢素浓度高得多的情况下,缓释胶囊的存活时间与每周玻璃体内注射的存活时间一样长。
用环孢素对眼睛进行局部免疫抑制可延长RPE异种移植物在兔视网膜下间隙的存活时间,这意味着排斥反应涉及活化的T淋巴细胞。用缓释胶囊进行局部免疫抑制与高得多浓度的每周注射一样有效。