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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.

白内障是全世界失明的主要原因。它们可能是由先天性突变引起的晶状体蛋白或由各种疾病（包括糖尿病）引起。我们最近研究了携带连接蛋白的小鼠模仿人类白内障相关突变的突变（Cx46fs380 和 Cx50D47A）。这些老鼠的镜片积累钙，形成与白内障相对应的沉淀物。我们假设生物矿化是白内障形成的一般机制。我们将表征钙的成分连接蛋白突变小鼠中的沉淀及其形成与白内障发展之间的关系。我们将测试是否有不同晶状体蛋白（γB-晶状体蛋白）突变的小鼠或实验性的小鼠诱发白内障还含有钙沉淀。该提案可能会深入了解基本原理白内障的致病机制并导致新的预防/治疗方法。