Aramant Robert B, Seiler Magdalene J
Departments of Ophthalmology and Visual Sciences, University of Louisville, Louisville, KY 40202, USA.
Exp Eye Res. 2002 Aug;75(2):115-25. doi: 10.1006/exer.2002.2001.
This study investigated whether transplanted sheets of human fetal retina together with its retinal pigment epithelium (RPE) could develop and maintain their cytoarchitecture after long survival times. Transplant recipients were nine albino athymic nu/nu rats with a normal retina. The donor tissue was dissected from fetuses of 12-17 weeks gestational age. Transplants were analyzed at 5-12 months after surgery by light and electron microscopy, and immunohistochemistry with various antibodies specific for rhodopsin, S-antigen, transducin, neurofilament and synaptophysin. In 4 of 11 transplants, the RPE stayed as a monolayer sheet and supported the development of the retinal sheet with a normal lamination, including photoreceptor inner and outer segments. Cones and rods in the organized transplants were labeled with different photoreceptor markers. Inner and outer plexiform layers, containing cone pedicles and rods spherules, were immunoreactive for synaptophysin. As the recipients had a normal retina, transplant/host integration was not expected. However, at the transplant/host interface, there were sometimes areas without glial barriers, and neurofilament-containing processes could be observed crossing between transplant and host. In other, more disorganized transplants, the RPE cells were partially dispersed or clumped together in clusters. Such transplants developed photoreceptors in rosettes, often with inner and outer segments. In conclusion, sheets of human fetal retina transplanted together with its RPE to the subretinal space of nude rats can develop and maintain perfectly laminated transplants after long survival times, indicating the potential of applying cotransplantation to human patients with retinal diseases.
本研究调查了移植的人胎儿视网膜及其视网膜色素上皮（RPE）片在长期存活后是否能够发育并维持其细胞结构。移植受体为9只视网膜正常的白化无胸腺裸大鼠。供体组织取自妊娠12 - 17周的胎儿。术后5 - 12个月，通过光学显微镜、电子显微镜以及使用针对视紫红质、S抗原、转导蛋白、神经丝和突触素的各种特异性抗体进行免疫组织化学分析移植情况。在11次移植中的4次，RPE保持为单层片，并支持具有正常分层的视网膜片的发育，包括光感受器内段和外段。组织化移植中的视锥细胞和视杆细胞用不同的光感受器标记物进行标记。包含视锥细胞终足和视杆细胞小球的内、外网状层对突触素呈免疫反应性。由于受体视网膜正常，预期不会出现移植/宿主整合。然而，在移植/宿主界面，有时存在没有胶质屏障的区域，并且可以观察到含有神经丝的突起在移植组织和宿主之间穿过。在其他更紊乱的移植中，RPE细胞部分分散或聚集成团。这样的移植形成了玫瑰花结样的光感受器，通常具有内段和外段。总之，将人胎儿视网膜及其RPE一起移植到裸鼠视网膜下间隙后，经过长时间存活，能够发育并维持结构完美分层的移植组织，这表明将共移植应用于患有视网膜疾病的人类患者具有潜力。
