Photoreceptor Signaling

We study photoreceptors in both health and disease, including electrical and biochemical signaling in rod and cone outer segments, the delicate interdependence of the photoreceptors with the Müller cells and RPE for healthy physiology, and rod circuitry in the retina.

I. Phototransduction

Rods are so sensitive that they can signal the absorption of a single photon, and we can use these electrical responses to understand how a single activated rhodopsin generates an amplified biochemical response.

From the electrophysiological responses to both dim and bright flashes, we can determine the active lifetime of photoexcited rhodopsin, the lifetime of the transducin-PDE complex, the basal rate of cGMP turnover, and calcium exchange currents in a wide variety of mouse models. We also use computational modeling to test our understanding and mechanistic interpretations.

II. Rod and Cone Physiology and Homeostasis

Normal photoreceptor signaling requires continual support of the RPE and Müller glia. For these reasons we are currently using both electrical and optical methodologies for studying both rods and cones in vivo.

We are also developing physiological metrics to assess photoreceptor stress, which in turn guides our experiments investigating why exaggerated phototransduction signaling causes cell death.

III. Retinal Circuitry

Rods and cones piggyback on many of the same types of bipolar cells, which makes teasing apart the relative contributions of rods and cones to signaling within any given downstream cell type challenging.