Regeneration of Retinal Neurons by Chemically Induced Reprogramming of Muller Gli

通过化学诱导 Muller Gli 重编程实现视网膜神经元再生

基本信息

批准号：
8730661
负责人：
SHENG DING
金额：
$ 83.13万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-09-30 至 2015-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8730661
关键词：
Adult Affect Age related macular degeneration Amacrine Cells Biological Assay Birds Blindness Cell Therapy Cells Chemicals Complex Embryonic Development Fishes Gene Expression Profile Generations Genes Human In Vitro Injury Light Mammals Modeling Molecular Muller&apos s cell Multipotent Stem Cells Mus Natural regeneration Neuroglia Neurons Pathway interactions Patients Pharmaceutical Preparations Photoreceptors Process Proliferating Protocols documentation Regenerative Medicine Research Retina Retinal Retinal Degeneration Retinal Photoreceptors Retinitis Pigmentosa Signal Transduction Stem cells Testing Therapeutic Transgenic Mice Transplantation Vertebrates Vision cell type ganglion cell high throughput screening in vitro Assay in vivo induced pluripotent stem cell novel photoreceptor degeneration pluripotency progenitor regenerative retinal damage retinal neuron retinal progenitor cell retinal rods small molecule small molecule libraries stem therapy development tool transdifferentiation visual stimulus

项目摘要

DESCRIPTION (provided by applicant): The retinal photoreceptors are the light-sensing cells that convert complex external visual stimuli to electrical and chemical signals. Degeneration of photoreceptors is the end point of the commonest causes of irreversible blindness including age-related macular degeneration and retinitis pigmentosa, affecting over 50 million people world-wide. In non-mammalian vertebrates such as fish, after retinal injury, resident Muller glia cells in the retina can proliferate, and differentiate into all retinal cell types including photoreceptors and restore visual functions. However, this regenerative potential is almost non-existent in mammals, with only very few new neurons generated after damage. We propose to develop and apply a high throughput screening to identify small molecules that will enhance Muller glia cells reprogramming and differentiation into retinal neurons in mammals, in vitro and in vivo. Identification, optimization, and characterizations of chemical tools for Muller cells reprogramming and differentiation will provide new avenues in developing cell-based therapy as well as conventional small molecule therapeutics for regenerative medicine, and facilitate new understanding of the transdifferentiation mechanisms. Our proposed research will facilitate the development of therapies to restore visual functions that have been lost in human patients with severe blindness.

描述（由申请人提供）：视网膜感受器是光感应细胞，这些细胞将复杂的外部视觉刺激转换为电信和化学信号。光感受器的变性是不可逆转的失明的最常见原因的终点，包括与年龄相关的黄斑变性和色素性视网膜炎，影响了全球超过5000万人。在视网膜损伤之后的非哺乳动物脊椎动物（如鱼类）中，视网膜中的常驻Muller Glia细胞可以增殖，并分化为所有视网膜细胞类型，包括光感受器和恢复视觉功能。但是，这种再生潜力在哺乳动物中几乎不存在，损伤后仅产生的新神经元很少。我们建议开发和应用高吞吐量筛选，以鉴定小分子，以增强穆勒胶质细胞的重编程和分化为哺乳动物，体外和体内的视网膜神经元。用于重编程和分化的化学工具的鉴定，优化和特征将为开发基于细胞的治疗以及用于再生医学的常规小分子疗法提供新的途径，并促进对转化机制的新理解。我们提出的研究将促进疗法的发展，以恢复患有严重失明的人类患者丧失的视觉功能。