Research in our lab aims to identify and characterize molecular genetic mechanisms that lead to cataract – a clinically important cause of visual impairment affecting the ocular lens. Typically, cataract is progressively acquired with aging (>40 years) as a complex trait with high heritability involving poorly understood gene-gene and gene-environment interactions. However, many genetic forms of cataract are known that present at an early age (birth-40 years) with or without systemic abnormalities and/or other ocular disorders. In particular, cataract may be inherited with abnormalities of anterior eye structures (cornea, iris, ciliary body and irridocorneal-angle drainage system) greatly increasing the risk for developing glaucoma – a blinding disease that progressively destroys the optic nerve. By studying genetic forms of cataract we hope to gain new insights about lens and anterior eye development, and to discover candidate genes for age-related cataract. So far we have identified mutations in 11 genes for inherited cataract; one of which is also associated with age-related cataract, and one with glaucoma.
Currently we have ongoing research projects in two complementary areas:
(1) Gene discovery: Genetic linkage analysis and targeted (exome) next-generation sequencing techniques are being used to (a) map and identify genes for inherited cataract, (b) develop diagnostic genetic tests for cataract and associated eye disorders, (c) identify risk variants in candidate genes for age-related cataract, and (d) identify the underlying gene in a mouse model of human age-related cataract.
(2) Functional expression studies: Gene-targeted mice are being used to model the roles of (a) receptor tyrosine kinase signaling in lens development and aging, (b) a novel cation channel in lens and anterior eye development, (c) a multi-vesicular endosome protein in lens development, and (d) ER-stress and apoptosis in cataract development.