Development of a cellular therapy for dry Age Related Macular Degeneration (AMD) using retinal pigment epithelium (RPE) derived from human embryonic stem cells (hESC)

干性老年性黄斑变性(AMD)是一种视网膜退行性疾病，会导致中心视力进行性下降。在德意志联邦共和国或美利坚合众国等国家，它是65岁以上老年人失明的主要原因，约有1200万名患者。它是由视网膜色素上皮(RPE)的细胞死亡引起的，RPE对维持健康的光感受器(PR)是不可或缺的，并与PR一起为视觉感知提供转导接口。我们假设丢失的RPE可以通过移植人类胚胎干细胞(HESC)在动物疾病模型中恢复。干细胞是早熟细胞和原始细胞，在基础研究项目中具有很大优势。它们通过细胞分裂具有很高的复制率，这得到了以下事实的支持：每个患者所需的细胞数量相对较少(1.5x105RPE)，这意味着通过工作和主细胞库很容易实现这一点。此外，每个细胞都有可能发育成成熟的RPE细胞。初步结果表明，hESC-RPE在视网膜营养不良动物模型中具有抗疾病作用。与加州理工大学合作，计划监测支持RPE的脉络膜毛细血管的血流动力学，并测量光感受器色素的变化。两者都是评价人胚胎干细胞移植RPE可行性的基本生理过程。

Dry age related macular degeneration (AMD) is a degenerative disease of the retina, which leads to a progressive decrease in central visual acuity. In countries like the Federal Republic of Germany or the United States of America it is the main reason of blindness for the over 65 aged with approximately 12 million patients. It is caused by the cell death of the retinal pigment epithelium (RPE), which is integral for maintenance of healthy photoreceptors (PR) and together with the PR provides the transducing interface for visual perception. We hypothesize that lost RPE can be restored in an animal disease model through transplantation with human embryonic stem cells (hESC). Stem cells are premature and primitve cells, that have a big advantage in the underlying research project. They bear a high replication rate through cell division, which is supported by the fact that there is the relative paucity of cell numbers needed for each patient (1.5x105 RPE) which means that it is easily achievable with working and master cell banks. Additionally each cell has the potential to develop to a mature RPE cell. Preliminary results demostrate that hESC have disease-modyfing activity of of hESC-RPE in animal models of retinal dystrophy. In cooperation with the CalTech university it is planned to monitor blood flow dynamics in the choriocapillaris that supports the RPE and to measure changes in the photoreceptor pigment. Both are essential physiologic processes to evaluate the feasibility of hESC transplanted RPE.