Rick H. Cote
Ph.D. University of Wisconsin at Madison, 1980
- Professor of Biochemistry and Molecular Biology
Vision, retina, visual transduction, phosphodieterase, cGMP metabolism, cyclic GMP, photoreceptors, rod photorepctor, cone photorecptor, phosphodiesterase inhibitor, pharmacology, protein chemistry, enzymology, neuroscience
Most blindness and visual disorders are caused by abnormal functioning of the photoreceptor cells (rods and cones) of the retina or by disorders of the underlying choroid. Important retinal disorders and diseases include: macular degeneration, congenital and developmental defects leading to retinal degeneration, retinitis pigmentosa, and damage caused by environmental agents or drugs. These conditions are known to affect both humans and many inbred strains of animals, including dogs, cats, pigs, chickens, mice, and rats. For most retinal diseases, there is neither means for a cure nor prevention. In economic terms, eye diseases and blindness cost the United States billions of dollars each year. Progress against these conditions depends on gaining new knowledge of the fundamental molecular and cellular processes underlying normal retinal function. Vision is triggered when light is absorbed by visual pigments contained in the rod and cone photoreceptor cells of the retina. Rods are able to convey visual information in dim light, while cones-being less sensitive-are ideally suited to operate in bright light conditions. In addition, different classes of cones exist in the retina, making possible wavelength discrimination and the perception of color.
Much is currently known about the biochemical pathway of visual transduction in rod photoreceptors. Activation of the visual pigment (rhodopsin) by light triggers a biochemical cascade resulting in the rapid decrease in guanosine-3',5'-cyclic monophosphate (cGMP) concentration. The enzyme catalyzing cGMP hydrolysis is the photoreceptor-specific cGMP phosphodiesterase (PDE). The decline in cGMP closes ion channels in the cell membrane, leading to the nerve impulse and the perception of a light stimulus. Regulation of the photoreceptor phosphodiesterase (PDE) is central to all aspects of phototransduction in that this enzyme plays a dominant role in determining cGMP levels in rod and cone photoreceptor outer segments. While the initial activation mechanism of PDE by the photoreceptor G-protein, transducin, has been extensively investigated in rod outer segments (ROS), the recovery and adaptational mechanisms that modulate the extent and lifetime of PDE activation need to be elucidated. In addition, several ROS proteins distinct from transducin interact with PDE, but their roles in regulating PDE activation and inactivation during phototransduction are not understood.
General Biochemistry Lab BCHM 659; Advanced Topic BCHM 960; Protein Structure & Function BCHM 794; Lab Biochem & Molecular Biology BCHM 755; Investigations BCHM 795; Senior Thesis BCHM 799