Prevention of Photoreceptor Degeneration

预防感光器退化

• 批准号: 6460359
• 负责人: RAYMOND D LUND
• 金额: $ 36.34万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-05-01 至 2006-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6460359
• 关键词: Schwann cells; cell line; cell transplantation; disease /disorder prevention /control; electron microscopy; gene mutation; genetically modified animals; laboratory mouse; laboratory rat; nonhuman therapy evaluation; retina degeneration; retinal pigment epithelium; transfection /expression vector; visual photoreceptor; xenotransplantation; Schwann cells; cell line; cell transplantation; disease /disorder prevention /control; electron microscopy; gene mutation; genetically modified animals; laboratory mouse; laboratory rat; nonhuman therapy evaluation; retina degeneration; retinal pigment epithelium; transfection /expression vector; visual photoreceptor; xenotransplantation

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.

它计划通过将细胞引入视网膜下空间来限制带有人类视紫红蛋白突变的转基因大鼠RCS大鼠中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细胞的替代方案在防止感光体变性的疗效，这是由于感光体本身或相邻RPE中的缺陷导致的。永生化的人RPE细胞系和雪旺氏细胞将用作供体细胞，将其移植到RCS大鼠或转基因大鼠中，并在Rhodopsin基因中具有突变，从而导致中等变性。 2）检查移植细胞如何在视网膜下空间中定位，它们如何与相邻细胞相互关联以及它们的生存时间。 3）检查移植细胞的数量和分布与光感受器拯救的程度相对应。 4）检查光感受器的救援与不幸的中央视觉功能如何相关。 5）使用移植细胞作为引入分子的载体。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（例如色素性视网膜炎和与年龄相关的黄斑变性）患者开发移植方法的可行性。其次，它还将接近变性和修复的基本生物学，这本身将提供有关可能影响光感受器存活的因素，并可能消除了作为潜在疗法的移植需求。