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 (?B-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.

Public Health Relevance

Cataracts are the major cause of blindness worldwide and of visual impairment in the United States. We have recently found that mutations of three different lens genes cause accumulation and precipitation of calcium in the lens corresponding to the cataracts in these animals. Studies are proposed to characterize these calcium precipitates and to determine the generality of calcium precipitation as a mechanism of cataract formation.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
1R01EY030914-01A1
Application #
10052015
Study Section
Biology of the Visual System Study Section (BVS)
Program Officer
Araj, Houmam H
Project Start
2020-09-01
Project End
2024-05-31
Budget Start
2020-09-01
Budget End
2021-05-31
Support Year
1
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of Chicago
Department
Pediatrics
Type
Schools of Medicine
DUNS #
005421136
City
Chicago
State
IL
Country
United States
Zip Code
60637