Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Biomaterials. 2010 Nov;31(31):7978-84. doi: 10.1016/j.biomaterials.2010.07.026. Epub 2010 Jul 24.
In retinal transplantation experiments it is hypothesized that remaining diseased photoreceptor cells in the host retina and inner retinal cells in transplants physically obstruct the development of graft-host neuronal contacts which are required for vision. Recently, we developed methods for the isolation of donor photoreceptor layers in vitro, and the selective removal of host photoreceptors in vivo using biodegradable elastomeric membranes composed of poly(glycerol-co-sebacic acid) (PGS). We also coated PGS membranes with electrospun nanofibers, composed of laminin and poly(epsilon-caprolactone) (PCL), to promote attachment of embryonic retinal explants, allowing the resulting composites to be handled surgically as a single entity. Here, we report subretinal transplantation of these composites into adult porcine eyes. In hematoxylin and eosin stained sections of composite explants after 5-7 days in vitro, excellent fusion of retinas and biomaterial membranes was noted, with the immature retinal components showing laminated as well as folded and rosetted areas. The composite grafts could be transplanted in all cases and, 3 months after surgery, eyes displayed clear media, attached retinas and the grafts located subretinally. Histological examination revealed that the biomaterial membrane had degraded without any signs of inflammation. Transplanted retinas displayed areas of rosettes as well as normal lamination. In most cases inner retinal layers were present in the grafts. Laminated areas displayed well-developed photoreceptors adjacent to an intact host retinal pigment epithelium and degeneration of the host outer nuclear layer (ONL) was often observed together with occasional fusion of graft and host inner layers.
在视网膜移植实验中，有假说认为宿主视网膜中的残留病变感光细胞和移植中的内视网膜细胞在物理上阻碍了移植宿主神经元接触的发育，而这些接触是视觉所必需的。最近，我们开发了体外分离供体感光层和体内选择性去除宿主感光细胞的方法，使用由聚（甘油-co-癸二酸）（PGS）组成的可生物降解弹性体膜。我们还在 PGS 膜上涂覆了由层粘连蛋白和聚（ε-己内酯）（PCL）组成的电纺纳米纤维，以促进胚胎视网膜外植体的附着，从而使所得复合材料可以作为一个整体进行手术处理。在这里，我们报告了将这些复合材料亚视网膜移植到成年猪眼中的情况。在体外培养 5-7 天后的复合材料外植体的苏木精和伊红染色切片中，注意到视网膜和生物材料膜的良好融合，未成熟的视网膜成分显示出分层以及折叠和玫瑰花结区域。在所有情况下都可以移植复合移植物，并且在手术后 3 个月，眼睛显示出清晰的介质、附着的视网膜和位于亚视网膜下的移植物。组织学检查显示生物材料膜已降解，没有任何炎症迹象。移植的视网膜显示出玫瑰花结区域以及正常的分层。在大多数情况下，移植物中存在内视网膜层。分层区域显示出与完整宿主视网膜色素上皮相邻的发育良好的感光细胞，并且经常观察到宿主外核层（ONL）的变性，同时偶尔会发生移植物和宿主内层的融合。
