Transport processes in photoreceptors

Medical University Of South Carolina, Charleston SC

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Abstract

DESCRIPTION (provided by applicant): Light activation of the vertebrate rod photoreceptor visual pigment rhodopsin requires the isomerization of the chromophore 11-cis retinal to the all-trans form. The regeneration of photosensitive rhodopsin containing 11-cis retinal is achieved through a series of reactions in the photoreceptors and retinal pigment epithelium. In photoreceptors, these steps include the hydrolysis of the protein-chromophore bond generating all-trans retinal, its subsequent reduction by retinol dehydrogenase to all-trans retinol, and removal of all-trans for further processing. Defects in these photoreceptor pathways have deleterious consequences for photoreceptor health and function. The long-term goal of this project is to understand the normal kinetic properties of these pathways and how specific mutations influence retinal processing. The kinetics of all-trans retinol formation and removal will be investigated in lower vertebrate and mouse photoreceptor preparations. As all-trans retinol is fluorescent, we will carry out these studies using fluorescence imaging of living photoreceptors with single and two-photon microscopy. The aims of the proposed research are to: (1) Determine the kinetics of all-trans retinol formation and removal in lower vertebrate photoreceptors. (2) Determine the kinetics of all-trans retinol formation in the photoreceptors of the normal mouse and in mouse models of clinical disorders. The regeneration of visual pigment underlies our ability to see continuously and under a wide range of light intensities. Defects in visual pigment regeneration have been implicated in a variety of retinal diseases ranging from impaired dark adaptation to complete blindness. The proposed research will determine which steps control retinoid processing in photoreceptors. It will also provide new information on how retinoid processing is affected in models of Stargardt's disease, an early onset form of macular degeneration, and Oguchi's disease, a form of stationary night blindness.