CELL BIOLOGY OF INHERITED RETINAL DEGENERATION

视杆外段（ROS）被视网膜色素上皮吞噬

Rod outer segment (ROS) phagocytosis by the retinal pigment epithelium (RPE) is essential for the maintenance of photoreceptors, however, the mechanism is not fully understood. One component that we have been studying is the ligand-receptor interaction. Our lab has been the first to identify a mannose receptor on the RPE apical surface which shares biochemical and immunological properties with the macrophage mannose receptor. We have shown that the ROS ligands for this receptor are rhodopsin and several other mannose-containing glycoproteins. Recently, we have shown that the mannose receptor on normal RPE is expressed on the apical membrane just before the onset of ROS phagocytosis (8 da.) and is retained throughout development. In RGS retinas, which show a greatly reduced ROS ingestion rate, mannose receptor is expressed at 8 days and is retained on the apical membrane only for one month before disappearing. In collaboration with Dr. Virginia Shepherd's lab at Vanderbilt University, who has cloned the macrophage mannose receptor, we are beginning to clone the rat RPE mannose receptor and are now in position to determine its primary structure and eventually identify any differences in the dystrophic receptor. The RCS retina will be useful in helping us achieve our long range goal, which is to elucidate the contribution of the man nose receptor to the mechanism of phagocytosis. To that end we must understand the cell biology of the mannose receptor during ROS binding and ingestion. We will determine the biosynthetic and turnover rates of the RPE mannose receptor and whether there are differences in the biosynthetic processing to its mature form in the RCS animals. Secondly, we will examine if the RPE man nose receptor is recycled after ROS phagocytosis. Thirdly, we will study whether the RPE mannose receptor is associated with the cytoskeleton during ROS binding and whether the mannose receptor in RCS animals is not linked to the cytoskeleton during binding. The fourth aim will determine what oligosaccharides are present on the mannose receptor and whether there are differences in the oligosaccharide structure of the RCS mannose receptor. The last aim will determine whether the mannose receptor of these two cell types is the product of a single gene, and whether there is a mutational basis for the phagocytic defect in RCS cells.