权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

The Roles of EYS in photoreceptor health

EYS 在感光器健康中的作用

基本信息

批准号：
10056405
负责人：
HUAIYU HU
金额：
$ 24.3万
依托单位：
UPSTATE MEDICAL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-01 至 2022-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10056405
关键词：
Animal Model Animals Applications Grants Biological Models Blindness Callithrix Callithrix jacchus jacchus Cell Therapy Cells Cilia Clinical Complex Development Disease Electroretinography Embryo Evaluation Extracellular Matrix Proteins Eye Female Future Generations Genes Genetic Diseases Genome Goals Health Homologous Gene Homologous Protein Housing Human Implant Investigational Therapies Knowledge Laboratories Litter Size Longitudinal Studies Maintenance Mammals Membrane Methods Modeling Mus Mutate Mutation Oocytes Ophthalmology Optical Coherence Tomography Photoreceptors Primates Proteins Protocols documentation Public Health Research Retina Retinal Degeneration Retinitis Pigmentosa Role Structure Study models Testing Translating Work Zebrafish assisted reproduction clinically relevant cone-rod dystrophy cost effective therapy fovea centralis genome editing knockout gene model development new therapeutic target nonhuman primate novel photoreceptor degeneration postnatal retinal imaging rodent genome therapeutic development therapeutic gene therapy development

项目摘要

Mutations in the secreted protein known as eyes shut homolog (EYS) make up a large number of autosomal recessive cases of cone-rod dystrophy and retinitis pigmentosa, retinal degeneration characterized by loss of photoreceptors. Interestingly, although present in most mammals, the rodent genome does not have a functional EYS locus. EYS protein in zebrafish is located near the connecting cilium, a structure that connects the inner and outer segment of photoreceptors and deletion of EYS causes photoreceptor degeneration in the zebrafish. Although EYS-deficient zebrafish does provide opportunities for mechanistic studies, it is a poor model for testing gene- or cell-based therapies for human retinal degeneration. This project is aimed at generating a novel EYS-deficient novel model essential for therapeutic development: Aim 1: Generation of a novel animal model bearing mutations in the EYS locus by genome editing. Aim 2: Evaluating retinal development and maturation by non-invasive assessments of structure and function: optical coherence tomography (OCT) and electroretinography (ERG). At the completion of the studies, we will have generated founder animals bearing mutations in the EYS locus. These animals will be used to generate a germline-transmitted EYS deficient retinal degeneration model in the future. They will be essential for testing gene- or cell-based therapies and for understanding how EYS deletion impacts the function and maintenance. In addition, robust protocols for non-invasive ophthalmologic and functional evaluations of the retina will be established for critical evaluation of retinal degeneration models in the future.

被称为闭眼同源物（EYS）的分泌蛋白中的突变占了很大一部分视锥-视杆细胞营养不良和视网膜色素变性的常染色体隐性病例中，以光感受器的丧失为特征。有趣的是，尽管存在于大多数哺乳动物中，啮齿动物基因组不具有功能性EYS基因座。斑马鱼的EYS蛋白位于连接纤毛，一种连接光感受器内外段的结构并且EYS的缺失导致斑马鱼的感光细胞退化。虽然眼睛缺陷斑马鱼确实为机制研究提供了机会，但它是测试基因或人类视网膜变性的细胞疗法。这个项目旨在创作一部小说治疗开发所必需的EYS缺陷新模型：目的1：通过基因组构建EYS基因座突变的新型动物模型编辑. 目的2：通过非侵入性评估评估视网膜发育和成熟，结构和功能：光学相干断层扫描（OCT）和视网膜电图（ERG）。在研究完成时，我们将产生携带以下突变的创始动物： EYS轨迹。这些动物将用于产生生殖系传播的EYS缺陷视网膜变性模型。它们对于检测基于基因或细胞的治疗和理解EYS缺失如何影响功能和维护。在此外，用于视网膜的非侵入性眼科和功能评估的稳健协议为今后视网膜变性模型的评价奠定了基础。