The interaction between the retinal pigment epithelium (RPE) and ten photoreceptor cells is critical for the maintenance of vision. One of the primary functions of the RPE is the phagocytosis and degradation of the shed tips of photoreceptor outer segments. Available evidence shows the phagocytosis of ROS by the RPE may be receptor-mediated, although a ROS-specific receptor has not been identified and ten cellular mechanisms involved in the phagocytic activation of RPE are not yet known. The objective of the proposed research is to define the cellular mechanisms which may be involved in regulation of phagocytosis in normal Long-Evans rat RPE. In addition, changes in protein kinase activity and protein phosphorylation will be evaluated in cultured RPE cells which are phagocytically challenged. Changes in the concentration of three second messengers, cyclic adenosine monophosphate, inositol triphosphate and diacylglycerol, which may regulate the phagocytic mechanism in RPE, will be assessed with different types of phagocytic challenge. Isolated ROS and polystyrene latex spheres (PSL) will be used as particles for phagocytic challenge to differentiate changes which are specific only for ROS uptake from changes which are common to both PSL and ROS interaction and may be non-specific. Results obtained using normal RPE will be compared to RPE cultures prepared from Royal College of Surgeons (RCS) rats which express a hereditary retinal degeneration. Compared to normal RPE, RCS RPE can phagocytize PSL equally as well, but show a reduced capacity for ROS phagocytosis. Difference between normal and RCS RPE phagocytically challenged with ROS may identify the components which are defective in the RCS strain and critical for normal phagocytosis. While the immediate goals are to define mechanisms related to phagocytic activation in rat RPE, information gained through these studies may be relevant to normal human RPE function and provide a basis for evaluating RPE function in some forms of human retinal degeneration.
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