The cell biology of phagocytic proteins in the retinal pigment epithelium.

摘要

A 175kDa mannose receptor has been identified in the apical membrane of rat and human retinal pigment epithelium (RPE) and has been shown to be involved in the process of retinal phagocytosis. The current studies were designed to further characterize the cell biology of the mannose receptor and other RPE proteins that may be involved in the phagocytosis of photoreceptor outer segments. The first study investigated the developmental expression of the mannose receptor protein in normal and phagocytic defective animals. Using immunofluroresence techniques, the mannose receptor is first detected in the apical RPE membrane of normal animals prior to outer segment differentiation and phagocytosis beginning at postnatal day (PND) 10 and remains present throughout postnatal development. In dystrophic RPE, the protein is present at PND8, however it begins to diminish by PND16 and is absent following PND26. In immunoblots of apical RPE membrane proteins, an immunoreactive 175 kDa protein is present, however, in all normal and dystrophic samples beginning at PND5. These data suggest that the mannose receptor is expressed in the RPE before the onset on specific phagocytosis and, by immunobiochemical techniques, appears to be altered in the dystrophic animal. The second, study investigated a 110kDa RPE protein. With several antibodies raised against the 162--175kDa macrophage mannose receptor, a 110kDa protein was also visualized in Western blots of rat, pig and human RPE protein samples. Because this protein cross-reacts with mannose receptor-specific antibodies it is speculated that the 110kDa may be structurally and perhaps functionally related to the larger, 175kDa mannose receptor. The final study was designed to investigate the presence of the sPLA2 receptor in RPE. This protein is structurally and functionally related to the mannose receptor. With immunohistochemical and molecular techniques, the data demonstrate that this protein is absent in RPE and is therefore not involved in retinal phagocytosis.