Prevention of Photoreceptor Degeneration

计划通过将细胞引入视网膜下腔来限制RCS大鼠中视网膜营养不良在具有人视紫红质突变的转基因大鼠中的有害后果。有五个具体目标。1)研究新鲜视网膜色素上皮细胞替代物在预防由于光感受器本身或邻近视网膜色素上皮缺陷引起的光感受器变性方面的功效。永生化的人RPE细胞系和许旺细胞将被用作供体细胞，将它们移植到RCS大鼠或具有导致中等变性率的视紫红质基因突变的转基因大鼠中。2)检查移植细胞如何在视网膜下腔中定居，它们如何与相邻细胞相互作用以及它们存活多久。3)研究移植细胞的数量和分布与光感受器拯救程度的关系。4)研究感光细胞拯救如何与保留的中央视觉功能相关。5)利用移植的细胞作为导入分子的载体。这项工作的目的是双重的。首先，它将提供必要的背景数据，以评估为视网膜变性疾病（如视网膜色素变性和年龄相关性黄斑变性）患者开发移植方法的可行性。其次，它还将探讨变性和修复的基本生物学，这本身将提供对可能影响光感受器生存的因素的见解，并可能消除将移植作为潜在疗法的需要。

It is planned to limit the deleterious consequences of retinal dystrophy in RCS rats in transgenic rats with human rhodopsin mutation by introducing cells to the subretinal space. There are five specific aims. 1) To study efficacy of alternatives to fresh RPE cells in preventing photoreceptor degeneration resulting from a defect in the photoreceptors themselves or in the adjacent RPE. Immortalized human RPE cell lines and Schwann cells will be used as donor cells, transplanting them either to RCS rats or to transgenic rats with mutations in the rhodopsin gene causing a moderate rate of degeneration. 2) To examine how grafted cells settle in the subretinal space, how they interrelate with adjacent cells and how long they survive. 3) To examine how numbers and distribution of grafted cells correspond with the degree of photoreceptor rescue. 4) To examine how photoreceptor rescue correlates with spared central visual function. 5) To use grafted cells as vectors for introduced molecules. The purpose of the work is twofold. First, it will provide essential background data necessary in assessing the feasibility of developing a transplantation approach for patients with retinal degenerative diseases such as retinitis pigmentosa and age related macular degeneration. Second, it will also approach the basic biology of degeneration and repair, which in itself will provide insights into factors that may influence photoreceptor survival and perhaps obviate the need for transplantation as a potential therapy.