The Roles of EYS in photoreceptor health

被称为闭眼同源基因(EYS)的分泌蛋白的突变构成了大量的 常染色体隐性遗传性视锥视杆细胞营养不良、视网膜色素变性、视网膜变性 以光感受器丧失为特征的。有趣的是，虽然存在于大多数哺乳动物中，但 啮齿动物的基因组没有一个功能性的EYS基因座。斑马鱼中的Eys蛋白位于 连接纤毛，一种连接光感受器内外节段的结构 而EYS的缺失会导致斑马鱼的光感受器退化。虽有眼亏 斑马鱼确实为机械研究提供了机会，但它是测试基因的一个糟糕的模型-或者 以细胞为基础的治疗人类视网膜变性。这个项目的目的是创作一部小说 对治疗发展至关重要的EYS缺陷新模式： 目的1：建立一种利用基因组检测EYS基因突变的动物模型 正在编辑。 目的2：通过非侵入性评估视网膜发育和成熟 结构与功能：光学相干断层扫描(OCT)和视网膜电图(ERG)。 在研究完成时，我们将产生携带突变的创始动物 眼睛的轨迹。这些动物将被用来产生生殖系传播的眼睛缺陷 视网膜退行性变模型的建立。它们将是基于基因或细胞的测试的关键 治疗和了解EYS缺失如何影响功能和维持。在……里面 此外，用于非侵入性眼科和视网膜功能评估的强大方案 将为未来视网膜退行性变模型的关键评估而建立。

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.