CELL BIOLOGY OF INHERITED RETINAL DEGENERATION

视网膜色素上皮对视杆细胞的吞噬作用 (RPE)对于维持光感受器是必不可少的，然而， 机制还没有完全弄清楚。我们一直以来的一个组成部分 研究的是配体-受体的相互作用。我们的实验室是第一个 鉴定RPE根尖表面的甘露糖受体 巨噬细胞甘露糖的生化和免疫学特性 受体。我们已经证明了这种受体的ROS配体是 视紫红质和其他几种含甘露糖的糖蛋白。最近， 我们已经证明，正常RPE上的甘露糖受体表达在 ROS吞噬开始前的顶膜(8d.)而且是 在整个发展过程中一直保留着。在RGS视网膜中，它显示出极大的 ROS摄取率降低，甘露糖受体在第8天表达， 仅在根尖膜上保留一个月 消失了。与弗吉尼亚·谢泼德博士的实验室合作 范德比尔特大学已经克隆了巨噬细胞甘露糖受体， 我们正在开始克隆大鼠RPE甘露糖受体，现在正在 定位以确定其主要结构并最终识别任何 营养不良受体的差异。RCS视网膜将在以下方面有用 帮助我们实现我们的长期目标，即阐明 人鼻受体在吞噬机制中的作用。 为此，我们必须了解甘露糖受体的细胞生物学。 在ROS结合和摄取过程中。我们将确定生物合成和 RPE甘露糖受体的周转率以及是否存在 RCS中生物合成过程中成熟形式的差异 动物。其次，我们将检查RPE人鼻子受体是否 在ROS吞噬后回收。第三，我们将研究RPE是否 在ROS结合过程中，甘露糖受体与细胞骨架相关 以及RCS动物中的甘露糖受体是否与 结合过程中的细胞骨架。第四个目标将决定 低聚糖存在于甘露糖受体上，以及是否有 RCS甘露糖的寡糖结构是否存在差异 受体。最后一个目标将决定甘露糖受体是否 这两种细胞类型是单一基因的产物，是否存在 是RCS细胞吞噬缺陷的突变基础。

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.