Abe Toshiaki, Yoshida Madoka, Yoshioka Yuki, Wakusawa Ryosuke, Tokita-Ishikawa Yumi, Seto Haruka, Tamai Makoto, Nishida Kohji
Division of Clinical Cell Therapy, Center for Translational and Advanced Animal Research, Tohoku University Graduate School of Medicine, Sendai, Japan.
Prog Retin Eye Res. 2007 May;26(3):302-21. doi: 10.1016/j.preteyeres.2007.01.003. Epub 2007 Jan 17.
The transplantation of different types of cells into the eye to treat retinal diseases has advanced in the past 20 years. One of the types of cells used for transplantation is the iris pigment epithelial (IPE) cell, because autologous IPE cells are easily obtained and their properties are similar to those of retinal pigment epithelial (RPE) cells and retinal cells. IPE cells are transplanted as; freshly isolated or cultured cells to replace defective or diseased RPE cells, genetically modified IPE cells for delivering target molecules to the retina or RPE, and retinal progenitor cells. IPE cells have also been transplanted for non-retinal disorders. The survival of the transplanted cells in the host is an important factor for the success of transplantation. Autologous IPE cells have been found in the transplanted subretinal space and were able to phagocytose rod outer segments even 6 months after transplantation. Allogeneic and xenogenic cells will not remain in the region longer than autologous cells. Allogenic cells transplanted into the subretinal space are rejected in humans. Thus, we have transplanted cultured autologous IPE cells in 56 patients with age-related macular degeneration. The long-term results (more than 2 years with a maximum of 8 years) showed that the visual acuity (VA) was significantly improved over the pre-transplantation VA, although a slight decrease of VA was observed 2 weeks after the transplantation. One patient showed a vasculitis-like lesion. IPE cells that were transduced with neurotrophic factors by plasmid or viral vectors have also been transplanted in animals. We have transduced several neurotrophic factor genes into IPE cells with a plasmid vector, adeno-associated virus, or adenovirus. Transplantation of these transduced IPE cells into the subretinal space rescued photoreceptor cells from several types of photoreceptor toxicities. In addition, transduction of a gene into the IPE cells suppressed the systemic dissemination of the viral genome. The neuroprotective effects of the IPE cells were different for the different types of neurotrophic factor, and some of the neurotrophic factors may enhance systemic immune reaction after transplantation. IPE cells have also been used as retinal progenital cells because they originate from the same cell lines that give rise to the neural retina and RPE cells. The transduction of the photoreceptor-related homeobox gene was reported to induce photoreceptor phenotypes in IPE cells. Furthermore, transplantations of IPE cells have been performed to treat central nervous system disorders. In this review, we summarize recent progress on IPE transplantation.
在过去20年中，将不同类型的细胞移植到眼睛中治疗视网膜疾病取得了进展。用于移植的细胞类型之一是虹膜色素上皮（IPE）细胞，因为自体IPE细胞易于获取，且其特性与视网膜色素上皮（RPE）细胞和视网膜细胞相似。IPE细胞作为以下几种形式进行移植：新鲜分离或培养的细胞，用于替代有缺陷或患病的RPE细胞；经过基因改造的IPE细胞，用于向视网膜或RPE递送靶分子；以及视网膜祖细胞。IPE细胞也已被用于非视网膜疾病的移植。移植细胞在宿主体内的存活是移植成功的一个重要因素。已发现自体IPE细胞存在于移植的视网膜下间隙中，甚至在移植6个月后仍能吞噬视杆细胞外节。同种异体和异种细胞在该区域停留的时间不会比自体细胞长。移植到视网膜下间隙的同种异体细胞在人类中会被排斥。因此，我们对56例年龄相关性黄斑变性患者进行了培养的自体IPE细胞移植。长期结果（超过2年，最长8年）表明，尽管在移植后2周观察到视力略有下降，但视力较移植前有显著改善。1例患者出现了血管炎样病变。通过质粒或病毒载体用神经营养因子转导的IPE细胞也已在动物中进行移植。我们已用质粒载体、腺相关病毒或腺病毒将几种神经营养因子基因转导到IPE细胞中。将这些转导的IPE细胞移植到视网膜下间隙可使光感受器细胞从几种类型的光感受器毒性中获救。此外，将基因转导到IPE细胞中可抑制病毒基因组的全身扩散。IPE细胞对不同类型神经营养因子的神经保护作用不同，并且一些神经营养因子可能会增强移植后的全身免疫反应。IPE细胞也被用作视网膜祖细胞，因为它们起源于与神经视网膜和RPE细胞相同的细胞系。据报道，光感受器相关同源框基因的转导可诱导IPE细胞出现光感受器表型。此外，还进行了IPE细胞移植以治疗中枢神经系统疾病。在本综述中，我们总结了IPE移植的最新进展。
