Patrick Dolph, Ph.D.

Research

Inherited retinal degeneration leads to vision loss in hundreds of thousands of people each year. Invertebrate photoreceptors respond to light via a G protein-coupled receptor/phosphatidylinositol signaling cascade. This visual transduction cascade is shut off, in part, by the binding of arrestin to the light receptor rhodopsin. We have found that in several different mutants that undergo retinal degeneration, this transient interaction between rhodopsin and arrestin is stabilized. The resulting rhodopsin/arrestin complexes are internalized into the cell body by receptor-mediated endocytosis. Once internalized, rhodopsin accumulates in specific intracellular compartments and induces cell death of the photoreceptor cells. Presently, we are using genetic, biochemical, and molecular techniques to dissect this cell death pathway and understand how the accumulation of these protein complexes in the cell body induces photoreceptor death. We have also established a Drosophila model for prion disease. We are presently using the powerful genetic tools of Drosophila to isolate modifiers of these phenotypes in an effort to understand the molecular basis of neuronal degeneration in prion disease.