Research Interests
Vision begins in photoreceptor cells with the activation by light of the visual pigment, rhodopsin. The exquisite sensitivity of our rod photoreceptors that enables us to see in dim to moderately bright light requires that rhodopsin is extremely stable and does not activate the rods in the absence of light. Recently, two mutations in rhodopsin have been identified that appear to compromise its stability: Glycine 90 to Aspartate (G90D) reported to cause congenital stationary night blindness (CSNB), and Glycine 90 to Valine (G90V) found in patients with retinitis pigmentosa (RP). Structural and biochemical in vitro studies have suggested that the G90D/G90V mutations cause lower stability of both chromophore-bound and chromophore-free rhodopsin. However, previous studies with transgenic animal models have yielded conflicting results about the form of rhodopsin responsible for its abnormally high activity. Thus, despite decades of research, the molecular mechanism by which these mutations cause abnormal photoreceptor function and degeneration remains a subject of debate and, as a result, effective treatments for people carrying these mutations are not available.

Using mice models, we will study heterozygous and homozygous G90D and G90V mutants, scenarios analogous to those in human patients to determine the effect of these two point mutations on rod morphology and degeneration (Aim 1). We will also evaluate the function of G90D and G90V mouse rods by in vivo electroretinography and single-cell suction electrode recordings (Aim 2). By studying side by side our G90D and G90V point mutant mice, we should be able to identify the mechanism by which they cause blindness. We should also be able to understand why these two similar mutations produce different clinical phenotypes.  Ultimately, our goal is to develop effective treatments targeted specifically towards patients carrying each of these two mutations and test their efficacy in human clinical studies.