Prevention of Photoreceptor Degeneration

计划通过将细胞引入视网膜下间隙，限制RCS大鼠视网膜营养不良的有害后果。有五个具体目标。1)研究新鲜RPE细胞的替代品在防止由光感受器本身或邻近RPE缺陷引起的光感受器变性方面的功效。永活的人类RPE细胞系和雪旺细胞将被用作供体细胞，将它们移植到RCS大鼠或具有视紫红质基因突变的转基因大鼠身上，造成中等程度的退化。2)观察移植细胞如何在视网膜下空间中沉淀，它们如何与相邻细胞相互作用，以及它们存活的时间。3)观察移植细胞的数量和分布与光感受器恢复程度的对应关系。4)探讨光感受器恢复与中枢视觉功能的相关性。5)利用移植物细胞作为导入分子的载体。工作的目的是双重的。首先，它将为评估视网膜退行性疾病（如视网膜色素变性和年龄相关性黄斑变性）患者移植方法的可行性提供必要的背景数据。其次，它也将接近退化和修复的基本生物学，这本身将提供对可能影响光感受器存活的因素的见解，并可能消除移植作为一种潜在治疗的需要。

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.