Background: Current concept of the visual pathway involves the formation of 11-cis retinol from all-trans retinyl esters by an isomerohydrolase. Both 11-cis retinal and 11-cis retinyl esters are derived from this 11-cis retinol and this branch point of the visual pathway is known. Although the fate of 11-cis retinal to serve as visual chromophore has been well studied, exactly how 11-cis retinyl esters are used to supply retinal chromophores for pigment regeneration is not known. Preliminary Studies: Previous studies conducted in our laboratory established the presence of an 11-cis retinyl ester hydrolase (REH) activity in the bovine retinal pigment epithelium (RPE) microsomes. Subcellular fractionation by sucrose and Percol gradients showed that 11- cis retinyl esters and hydrolase enzyme activity are co-localized at the plasma membrane (PM). Hypothesis: These data support the hypothesis that in the RPE PM, there is an 11-cis REH enzyme. This enzyme may control a novel, unexplored branch of the visual pathway to supply visual chromosomes for visual pigment regeneration. Methods: We propose to extend our current research to include complete purification and biochemical characterization of this 11-cis REH enzyme. When a sufficient amount of this protein is available, polyclonal antibody will be raised and immunofluorescence method will be used to study the localization of this enzyme in the RPE. Biomedical Relevance: This research is important because details of this branch of the visual pathway is completely lacking. Results from studies on the control of 11-cis retinyl ester hydrolysis could provide rationale for understanding those ocular diseases associated with a reduction of visual sensitivity and/or delays in the time course of bleaching recovery.