虹膜色素上皮移植

自体虹膜色素上皮容易获得，能够吞噬光感受器外节盘膜，使得用它替代视网膜色素上皮细胞移植到视网膜下腔以治疗视网膜色素上皮变性疾病成为可能。对IPE和视网膜色素上皮(RPE)细胞的功能进行了比较，并对IPE细胞的培养方法，用IPE细胞移植治疗老年性黄斑变性和视网膜色素变性等技术进行了综述。     

自体虹膜色素上皮细胞移植治疗视网膜色素上皮细胞变性研究

目的:研究自体虹膜色素上皮细胞(iris pigment epithelium,IPE)移植治疗视网膜色素上皮细胞变性的效果。方法:采用酶-机械分离-酶消化法获取高纯度、高活力的IPE细胞用于移植,采用外路法将IPE细胞悬液移植入视网膜下腔。结果:IPE移植术后患者眼底移植区色素沉着减少,未见渗出,出血,视网膜平,视力入院时的0.15,术后2wk提高至0.2。多焦ERG显示移植区P1波平均反应密度上升。结论:自体虹膜色素上皮细胞移植有望成为视网膜色素上皮细胞变性疾病治疗的一新方法。     

Iris pigment epithelial cell transplantation for degenerative retinal diseases

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.     

视网膜色素上皮移植最新进展

视网膜色素上皮细胞移植是近年治疗视网膜变性疾病的一个引人注目的领域。目前视网膜色素上皮移植技术已逐步应用于临床。现就视网膜色素上皮细胞移植的供体材料选择、受体要求、目的基因导入及其临床应用的最新进展作一综述。[眼科新进展2005；25（5）：470—472]     

视网膜色素上皮细胞的诱导分化及其移植治疗方法的研究进展

视网膜色素上皮(retinal pigment epithelium,RPE)的病变可以导致多种视网膜疾病,目前缺乏有效的治疗手段.人类多能干细胞具有多向分化潜能,为此类疾病的细胞治疗提供了理想来源.本文将近年来胚胎干细胞和诱导多能干细胞体外定向分化为RPE细胞及移植治疗年龄相关性黄斑变性等视网膜疾病的研究进行了综述.     

视网膜色素上皮细胞的诱导分化及其移植治疗方法的研究进展

视网膜色素上皮(retinal pigment epithelium,RPE)的病变可以导致多种视网膜疾病,目前缺乏有效的治疗手段.人类多能干细胞具有多向分化潜能,为此类疾病的细胞治疗提供了理想来源.本文将近年来胚胎干细胞和诱导多能干细胞体外定向分化为RPE细胞及移植治疗年龄相关性黄斑变性等视网膜疾病的研究进行了综述.     

Stem cells as source for retinal pigment epithelium transplantation

Inherited maculopathies, age related macular degeneration and some forms of retinitis pigmentosa are associated with impaired function or loss of the retinal pigment epithelium (RPE). Among potential treatments, transplantation approaches are particularly promising. The arrangement of RPE cells in a well-defined tissue layer makes the RPE amenable to cell or tissue sheet transplantation. Different cell sources have been suggested for RPE transplantation but the development of a clinical protocol faces several obstacles. The source should provide a sufficient number of cells to at least recover the macula area. Secondly, cells should be plastic enough to be able to integrate in the host tissue. Tissue sheets should be considered as well, but the substrate on which RPE cells are cultured needs to be carefully evaluated. Immunogenicity can also be an obstacle for effective transplantation as well as tumorigenicity of not fully differentiated cells. Finally, ethical concerns may represent drawbacks when embryo-derived cells are proposed for RPE transplantation. Here we discuss different cell sources that became available in recent years and their different properties. We also present data on a new source of human RPE. We provide a protocol for RPE differentiation of retinal stem cells derived from adult ciliary bodies of post-mortem donors. We show molecular characterization of the in vitro differentiated RPE tissue and demonstrate its functionality based on a phagocytosis assay. This new source may provide tissue for allogenic transplantation based on best matches through histocompatibility testing.     

Ageing of the retinal pigment epithelium: implications for transplantation

This review will discuss some of the implications for using cells from aged donors for retinal pigment epithelium (RPE) transplantation. It will consider age-related changes in the structure and function of RPE cells and the accumulation of potentially damaging photoreactive constituents. The review will focus on the role of the ocular pigments lipofuscin and melanin in respect to age-related changes in composition, photoreactivity and potential role in retinal ageing and age-related macular degeneration. The article concludes by considering the suitability of senescent RPE cells for transplantation and whether such cells can be rejuvenated.     

视网膜色素上皮移植细胞超微结构的观察

目的 观察视网膜色素上皮移植细胞的超微结构,为临床应用提供实验基础。方法 取有色兔眼球后段,去除视网膜的神经上皮层,获得视网膜色素上皮细胞作为移植的供体细胞。以１０只无色兔为移植的受体,内路法将供体色素上皮细胞移植到视网膜下腔,电镜观察移植细胞的超微结构。结果 移植的１０只眼,细胞成功移植到视网膜下腔,可见移植细胞粘附于受体的Ｂｒｕｃｈ膜并形成基底内褶,细胞间紧密连接,细胞内可见吞噬体。结论 内路     

Photoreceptor rescue in the RCS rat without pigment epithelium transplantation

Transplantation of normal retinal pigment epithelium (RPE) to the subretinal space has been reported to rescue photoreceptors in the RCS rat. Moreover, the rescue effect was surprisingly large considering the relatively small number of RPE cells transplanted. The reason for this widespread rescue of photoreceptors is not known, nor is the mechanism for outer segment phagocytosis in photoreceptors not apposed to the transplanted RPE cells. This suggests that the rescue effect may not be solely mediated by the transplanted cells. We therefore wished to test whether the transplantation surgery itself might contribute to the rescue of RCS photoreceptors. For these control experiments, we performed the surgery on juvenile RCS rats as described by others for the transplantation of RPE but instead of injecting RPE, we injected saline. We sacrificed the RCS control operates two months following surgery. In the area of the surgery (superior retinal quadrant) the outer nuclear layer (ONL) was up to 8-10 photoreceptor cells thick, while at the extreme inferior margin of the retina the ONL was almost eliminated. To investigate the role of temporary retinal detachment in photoreceptor rescue we repeated the above experiment using our trans-corneal approach to the subretinal space. This procedure results in a large temporary retinal detachment and little or no damage to the choroid and sclera.(ABSTRACT TRUNCATED AT 250 WORDS)     

Retinal pigment epithelium tears after intravitreal bevacizumab in pigment epithelium detachment

PURPOSE: To evaluate pigment epithelium detachment (PED) secondary to exudative age-related macular degeneration (AMD) treated with intravitreal injection of bevacizumab with regard to incidence of retinal pigment epithelium tears (RIPs). DESIGN: Retrospective, interventional case series. METHODS: Institutional study of 31 eyes with PED in exudative AMD receiving intravitreal bevacizumab. Main outcome measures were Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuity, PED vascularization and size measured by angiography and optical coherence tomography (OCT) imaging, and incidence of RIP. RESULTS: Vision improved in six eyes and remained stable in 22 eyes (follow-up, 12.3 +/- 10.3 weeks). Twenty-eight eyes showed a vascularized PED. Four eyes (12.9%) experienced an RIP without vision loss. All RIP cases were vascularized in more than 50% of total lesion size. CONCLUSIONS: In short-term follow-up, the risk for RIP after bevacizumab injection in eyes with PED seems to be moderately, but not statistically significantly, increased in PED lesions vascularized more than 50%.     

Retinal pigment epithelium transplantation: concepts,challenges, and future prospects

The retinal pigment epithelium (RPE) is a single layer of cells that supports the light-sensitive photoreceptor cells that are essential for retinal function. Age-related macular degeneration (AMD) is a leading cause of visual impairment, and the primary pathogenic mechanism is thought to arise in the RPE layer. RPE cell structure and function are well understood, the cells are readily sustainable in laboratory culture and, unlike other cell types within the retina, RPE cells do not require synaptic connections to perform their role. These factors, together with the relative ease of outer retinal imaging, make RPE cells an attractive target for cell transplantation compared with other cell types in the retina or central nervous system. Seminal experiments in rats with an inherited RPE dystrophy have demonstrated that RPE transplantation can prevent photoreceptor loss and maintain visual function. This review provides an update on the progress made so far on RPE transplantation in human eyes, outlines potential sources of donor cells, and describes the technical and surgical challenges faced by the transplanting surgeon. Recent advances in the understanding of pluripotent stem cells, combined with novel surgical instrumentation, hold considerable promise, and support the concept of RPE transplantation as a regenerative strategy in AMD.     

Autologous transplantation of retinal pigment epithelium after mechanical debridement of Bruch's membrane

PURPOSE: To determine whether transplantation of autologous retinal pigment epithelium (RPE) will prevent atrophy of the choriocapillaris and loss of photoreceptors in an area in which the RPE has been mechanically debrided from Bruch's membrane. METHODS: Abrasive debridement of RPE was performed with a metal cannula after localized retinal bleb detachments in two separate areas of the rabbit retina. The RPE cell suspension aspirated from one of the debridement sites was transplanted to the other. The debridement-only site served as control. The transplant and control sites were evaluated after 30 days by color fundus photography, fluorescein angiography, light microscopy and transmission electron microscopy. RESULTS: Compared with debridement only, debridement plus transplantation of RPE resulted in more complete repopulation of the bare Bruch's membrane surface with relative preservation of choriocapillaris and photoreceptors. CONCLUSION: Autologous transplantation of RPE onto an abrasively debrided Bruch's membrane decreases choriocapillaris atrophy and photoreceptor loss.