The long-term goal of this research is the understanding of the biochemical processes underlying light transduction in cone photoreceptors, the retinal cells responsible for seeing at high light intensities. The most extensively studied photoreceptors are the rods, which are responsible for seeing at low light intensities. Both rods and cones utilize cyclic GMP (cGMP) as the internal transmitter that mediates the conversion of light into an electrical signal. Compared to rods, cones are less sensitive and respond faster to light. These differences are thought to be due to differences in the enzymatic machinery of the two cell types, although specific information is lacking for the cone photoreceptor enzymes. This project will employ electrophysiological methods to characterize the activities of the cGMP-metabolizing enzymes in single cone outer segments.
The specific aims are: (1) Characterization of the cGMP-activated channels. (2) Characterization of the guanylate cyclase, the enzyme producing cGMP. (3) Characterization of the phosphodiesterase, the light-sensitive enzyme hydrolyzing cGMP. The significance of the project lies in the characterization of the biochemical processes that underlie the ability of cones to function at high light intensities. The proposed electrophysiological approach is almost unique for the successful pursuit of its objectives, since the limited availability of retinas rich in cone outer segments has hindered biochemical studies of the cone phototransduction machinery. The quantitative understanding of the biochemical basis of the visual transduction process in cones will significantly improve our knowledge of the physiology of the retina. Such knowledge will contribute to our understanding of retinal degeneration diseases, especially cone-related ones, like cone dystrophies.
