Center for Regenerative Therapies Dresden, Technische Universität Dresden, Germany.
Werner Reichardt Centre for Integrative Neuroscience and Bernstein Center for Computacional Biology, Universität Tübingen, Tübingen, Germany.
Invest Ophthalmol Vis Sci. 2014 Aug 7;55(8):5431-44. doi: 10.1167/iovs.14-14325.
Age-related macular degeneration (AMD) is a major leading cause of visual impairment and blindness with no cure currently established. Cell replacement of RPE is discussed as a potential therapy for AMD. Previous studies were performed in animal models with severe limitations in recapitulating the disease progression. In detail, we describe the effect of systemic injection of sodium iodate in the mouse retina. We further evaluate the usefulness of this animal model to analyze cell-specific effects following transplantation of human embryonic stem cell (hESC)-derived RPE cells.
Morphologic, functional, and behavioral changes following sodium iodate injection were monitored by histology, gene expression analysis, electroretinography, and optokinetic head tracking. Human embryonic stem cell-derived RPE cells were transplanted 1 week after sodium iodate injection and experimental retinae were analyzed 3 weeks later.
Injection of sodium iodate caused complete RPE cell loss, photoreceptor degeneration, and altered gene and protein expression in outer and inner nuclear layers. Retinal function was severely affected by day 3 and abolished from day 14. Following transplantation, donor hESC-derived RPE cells formed extensive monolayers that displayed wild-type RPE cell morphology, organization, and function, including phagocytosis of host photoreceptor outer segments.
Systemic injection of sodium iodate has considerable effects on RPE, photoreceptors, and inner nuclear layer neurons, and provides a model to assay reconstitution and maturation of RPE cell transplants. The availability of an RPE-free Bruch's membrane in this model likely allows the unprecedented formation of extensive polarized cell monolayers from donor hESC-derived RPE cell suspensions.
年龄相关性黄斑变性（AMD）是导致视力损害和失明的主要原因，但目前尚无治愈方法。RPE 细胞替代被认为是 AMD 的一种潜在治疗方法。以前的研究是在动物模型中进行的，这些模型在重现疾病进展方面存在严重的局限性。具体来说，我们描述了在小鼠视网膜中全身注射碘酸钠的效果。我们进一步评估了该动物模型在分析人胚胎干细胞（hESC）衍生的 RPE 细胞移植后细胞特异性效应方面的有用性。
通过组织学、基因表达分析、视网膜电图和视动头跟踪监测碘酸钠注射后的形态、功能和行为变化。在注射碘酸钠后 1 周进行 hESC 衍生的 RPE 细胞移植，并在 3 周后分析实验性视网膜。
碘酸钠注射导致 RPE 细胞完全丧失、光感受器变性以及外核层和内核层的基因和蛋白表达改变。视网膜功能在第 3 天受到严重影响，并在第 14 天被废除。移植后，供体 hESC 衍生的 RPE 细胞形成了广泛的单层，显示出野生型 RPE 细胞的形态、组织和功能，包括对宿主光感受器外节的吞噬作用。
全身注射碘酸钠对 RPE、光感受器和内核层神经元有很大的影响，并提供了一个用于检测 RPE 细胞移植重建和成熟的模型。在该模型中，RPE 缺乏 Bruch 膜，这可能允许从供体 hESC 衍生的 RPE 细胞悬浮液中形成前所未有的广泛极化细胞单层。
