GENE THERAPY FOR TREATMENT OF RETINAL DEGENERATION

治疗视网膜变性的基因疗法

• 批准号: 6138143
• 负责人: Horst A. von Recum
• 金额: $ 3.24万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-12-17 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6138143
• 关键词: gene expression; gene targeting; gene therapy; laboratory rat; method development; retina degeneration; retinal pigment epithelium; tissue /cell culture; tissue engineering; visual photoreceptor

The delivery of cytokines into the subretinal space may play an important role in the treatment of retinal degenerative diseases such as age related macular degeneration and certain forms of retinitis pigmentosa. These diseases, which constitute the leading cause of adult onset blindness spring from a variety of genetic sources, and have few available treatment options. Transplantation of retinal cells, as well as delivery of genes to restore lost function are currently being investigated both in the laboratory and clinical setting as possible treatments. This proposal combines elements of both procedures with the goal of long-term drug delivery into the subretinal space. Preliminary research has shown that single dose injection of cytokines into the eye show short-term prevention of photoreceptor degeneration in rat disease models. In order to achieve long-term delivery and prevention we propose the use of genetically modified cells which can overexpress the desired cytokines upon external pharmacological signaling. The method of action of these primarily neurotrophic cytokines could be simultaneously in the photoreceptor and the retinal pigmented epithelium (RPE). We propose that these biomolecules cause upregulation in photoreceptor metabolism, maintaining viable pre-dystrophic levels of gene expression. In the RPE upregulation prevents dedifferentiation into a wound-healing phenotype allowing maintenance of the immunoisolating blood-retina barrier. We intend to use the genetically altered transplant model to investigate these two hypotheses, following photoreceptor rescue and cellular metabolism. The long term goal of this project is to provide tissue engineering therapy which can be applicable to retinal dystrophies with differing etiology.

将细胞因子输送到视网膜下空间可能会发挥作用 在视网膜退行性疾病的治疗中的重要作用 作为年龄相关的黄斑变性和某些形式的视网膜炎 色素 这些疾病构成了成人的主要原因 从各种遗传来源发作的失明春季，很少 可用的治疗选择。视网膜细胞的移植 作为递送基因以恢复功能损失的功能 尽可能在实验室和临床环境中进行研究 治疗。 该提案结合了这两个程序的要素和 长期药物输送到视网膜下空间的目标。 初步的 研究表明，单剂量注射细胞因子进入眼睛 显示大鼠疾病中光感受器变性的短期预防 型号。 为了实现长期交付和预防，我们 提出使用转基因细胞的使用，可以过表达 外部药理信号传导上所需的细胞因子。 该方法 这些主要是神经营养细胞因子的作用可能是 同时在感光器和视网膜色素上皮中 （RPE）。 我们建议这些生物分子在 光感受器代谢，维持可行的前营养性水平 基因表达。 在RPE上调可以防止去分化 进入伤口治疗表型，可以维护 免疫分散的血液隔离屏障。 我们打算在遗传上使用 改变了移植模型以研究这两个假设， 感光器救援和细胞代谢。 长期目标的 该项目是提供可以提供的组织工程疗法 适用于具有不同病因的视网膜营养不良。