The Roles of EYS in photoreceptor health

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。

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.