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Geobiology of Cataracts

白内障的地球生物学

基本信息

批准号：
10229612
负责人：
VIVIANA M BERTHOUD BARRANDEGUY
金额：
$ 52.55万
依托单位：
UNIVERSITY OF CHICAGO
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 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10229612
关键词：
Animals Anions Appearance Blindness Blood Circulation Buthionine Sulfoximine Calcium Calcium ion Cataract Cells Confocal Microscopy Connexins Crystallins Crystallization Data Defect Deposition Development Diabetes Mellitus Disease Dyes Electron Microscopy Environmental Risk Factor Etiology Event Excision Functional disorder Gene Mutation Genes Homeostasis Human Immunoblotting Immunofluorescence Immunologic In Vitro Ions Lead Learning Lens Fiber Light Link Lipids Maintenance Mass Spectrum Analysis Microscopy Minerals Mus Mutant Strains Mice Mutation Nutrient Operative Surgical Procedures Organ Oxidation-Reduction Pathogenicity Pathologic Patients Precipitation Process Prosthesis Proteins Publications Retina Risk Roentgen Rays Salts Series Solubility Spectrum Analysis Stains Streptozocin Systemic disease Testing Therapeutic Time Tissues United States Visual impairment Visual system structure Water X-Ray Computed Tomography age related biomineralization calcification congenital infection experimental study gap junction channel human model innovation insight intercellular communication lens lens transparency light transmission microCT mouse model mutant new technology novel novel therapeutics operation prevent sight restoration

项目摘要

Cataracts are the leading cause of blindness worldwide. They can be caused by congenital mutations of lens proteins or by various diseases including diabetes. We have recently studied mice carrying connexin mutations (Cx46fs380 and Cx50D47A) that mimic human cataract-linked mutations. The lenses of these mice accumulate calcium which forms precipitates that correspond to the cataracts. We hypothesize that bio- mineralization is a general mechanism of cataract formation. We will characterize the composition of calcium precipitates in connexin mutant mice and the relation between their formation and cataract development. We will test whether mice with mutations of a different lens protein (γB-crystallin) or mice with experimentally- induced cataracts also contain calcium precipitates. This proposal may give insights into fundamental pathogenic mechanisms of cataracts and lead to new preventative/therapeutic approaches.

白内障是世界范围内导致失明的主要原因。它们可能是由先天突变引起的晶状体蛋白或包括糖尿病在内的各种疾病。我们最近研究了携带连接蛋白的小鼠与人类白内障相关的突变(Cx46fs380和Cx50D47A)。这些小鼠的晶状体积累钙，形成与白内障相应的沉淀物。我们假设生物- 成矿作用是白内障形成的一般机制。我们将对钙的组成进行表征连接蛋白突变小鼠中的沉淀物及其形成与白内障发生的关系。我们将测试一种不同晶状体蛋白突变的小鼠(γB-晶体蛋白)或实验小鼠- 诱发性白内障也含有钙沉淀物。这一建议可能会让人们对基本的白内障的致病机制，并导致新的预防/治疗方法。