Approximately 50 million people worldwide are blind and ~150 million are significantly vision-impaired. Except for trauma and infections, the majority of human eye diseases are genetic in nature. Initially, the goal of our research program was to use mouse models as an entry point to identify the molecules that were essential for normal retinal development and function through positional cloning efforts. We have identified the molecular basis of >100 models, discovered through spontaneous and chemically induced screening.
With the maturation of our program, we have begun to focus on using these models to study gene function and mechanisms underlying disease pathology. Knowledge of genetic modifiers and interaction partners is critically important in understanding the pathways that lead from a primary genetic defect to an observable phenotype. The overriding theme of our program currently is the elucidation of interactions that occur among molecules to identify common functional pathways as well as pathways that lead to disease and are impacted by primary mutations. We employ a blend of marker analyses, noninvasive imaging, functional studies, and generation of mouse resources that aim toward a greater understanding of the function and pathways in which the mutant retinal molecules we have identified act.