Molecular Pathology of Achromatopsia

全色盲的分子病理学

基本信息

批准号：
10148846
负责人：
JONATHAN LIN
金额：
$ 30.17万
依托单位：
STANFORD 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：
2020-02-20 至 2021-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10148846
关键词：
Molecular Pathology Achromatopsia

项目摘要

Achromatopsia is a heritable, blinding disease characterized by cone photoreceptor dysfunction and retinal degeneration. Using next-generation sequencing, we discovered novel mutations in the ATF6 gene in patients with achromatopsia. ATF6 is an important regulator of the Unfolded Protein Response, an intracellular molecular mechanism that protects cells from protein misfolding and endoplasmic reticulum stress. The function of ATF6 in photoreceptors and the mechanism by which human ATF6 mutations cause cone dysfunction, photoreceptor cell death, and achromatopsia are unknown. The objective of this proposal is to determine how ATF6 regulates photoreceptor cell survival, and why mutations in ATF6 cause retinal degeneration in patients. To understand the role of ATF6 stress in retinal degeneration, we will: 1. Determine the role of ATF6 in human retinal development, 2. Determine the mechanism of retinal degeneration in Atf6-/- mice. 3. Identify the biochemical mechanism for the pathogenicity of human ATF6 mutations. ATF6 is a novel gene required for healthy retinal function in people. Our research is expected to elucidate the function of ATF6 in photoreceptors under normal and diseased conditions. Our studies will have a positive impact by revealing why ATF6 mutations cause vision loss and identify new environmental and pharmacologic strategies to prevent retinal degeneration in affected individuals.

Achromomatia是一种可遗传的，令人眼花疾病的疾病，具有锥形光感受器功能障碍和视网膜退化。使用下一代测序，我们在患者的ATF6基因中发现了新的突变与Achromomatia。 ATF6是展开蛋白质反应的重要调节剂，细胞内可保护细胞免受蛋白质折叠和内质网应激的分子机制。这 ATF6在感光体中的功能以及人ATF6突变引起锥体的机制功能障碍，感光细胞死亡和Achromomatia尚不清楚。该提议的目的是确定ATF6如何调节感光细胞存活，以及为什么ATF6中的突变引起视网膜患者退化。要了解ATF6应力在视网膜变性中的作用，我们将：1。 ATF6在人类视网膜发育中的作用，2。确定视网膜变性的机理 ATF6 - / - 小鼠。 3。确定人ATF6突变致病性的生化机制。 ATF6是人类健康视网膜功能所需的一种新型基因。我们的研究有望阐明在正常和患病状况下，ATF6在感光体中的功能。我们的研究将有积极的通过揭示为什么ATF6突变会导致视力丧失并确定新的环境和药理学来影响预防受影响个体视网膜变性的策略。