The Roles of EYS in photoreceptor health

被称为闭眼同源物 (EYS) 的分泌蛋白的突变占了很大一部分 常染色体隐性遗传的视锥杆营养不良和色素性视网膜炎、视网膜变性病例 其特征是光感受器丧失。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，一种连接感光器内段和外段的结构 EYS 的缺失会导致斑马鱼的光感受器退化。虽然 EYS 缺乏 斑马鱼确实为机械研究提供了机会，但它对于测试基因或基因来说是一个糟糕的模型 针对人类视网膜变性的细胞疗法。该项目旨在产生一种新颖的 EYS 缺陷的新模型对于治疗开发至关重要： 目标 1：通过基因组产生 EYS 位点突变的新型动物模型 编辑。 目标 2：通过非侵入性评估来评估视网膜发育和成熟度 结构和功能：光学相干断层扫描（OCT）和视网膜电图（ERG）。 研究完成后，我们将产生携带突变的创始人动物 EYS 基因座。这些动物将被用来产生种系传播的 EYS 缺陷 未来的视网膜变性模型。它们对于测试基于基因或细胞的药物至关重要 疗法并了解 EYS 缺失如何影响功能和维持。在 此外，用于非侵入性眼科和视网膜功能评估的强大协议 将建立用于未来视网膜变性模型的严格评估。

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.