Lens connexins, cellular stress, and cataracts (NEI R56)
Amount
Not specified
Deadline✓ Verified
Aug 31, 2027
Funder
National Eye Institute
Eligible
open to all
About This Grant
Cataracts are the leading cause of blindness worldwide. They are frequently associated with aging, but they can be caused by congenital mutations of lens proteins or by various diseases including diabetes. The prevailing dogma is that cataracts are caused by the accumulation of damage to lens components (especially proteins). We have found that mice carrying mutations of the lens fiber cell connexins (connexin46 and connexin50) or γC-crystallin have abnormalities of lens ionic homeostasis; these alterations lead to the formation of calcium-containing precipitates in the same region and distribution as the cataracts. We have also found that the insoluble material from cataract surgeries contains calcified particles. These findings implicate the disruption of ionic homeostasis and formation of calcified deposits as general processes contributing to cataract formation. In the proposed studies, we will utilize human lens material, mutant mice, and an in vitro model to define additional fac
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