Mannose 6-phosphate receptors on the plasma membrane on rat retinal pigment epithelial cells.

The retinal pigment epithelium (RPE) phagocytizes the tips of photoreceptor outer segments (OS) during normal eye function. It is not known what ligand on OS is recognized by the RPE for removal from the interphotoreceptor matrix. It is possible that a sugar residue on a cell surface glycoconjugate of either the OS or RPE mediates the phagocytic interaction. Pinocytic experiments with a soluble mannose 6-phosphate ligand (125I-labelled mannosidase) showed that similar quantities of ligand were bound by RPE explants from Long Evans rat retinas and from Royal College of Surgeons (RCS/p+) rat retinas known to be defective in the phagocytosis of OS. The addition of mannose 6-phosphate reduced the total counts of bound alpha-mannosidase by 23% in both normal and dystrophic RPE explants. Mannose 6-phosphate receptors were visualized on normal and dystrophic RPE plasma membranes by immunocytochemical techniques. Further, phagocytosis was studied using phosphomannan-coated beads as phagocytic particles. Dystrophic RPE phagocytized phosphomannan-coated beads by a mannose 6-phosphate specific mechanism as shown by a significant reduction in the number of these coated beads taken up in the presence of the competing sugar. In contrast, normal RPE showed no uptake of phosphomannan-coated beads. Our findings indicate that a mannose 6-phosphate receptor is on the apical plasma membrane of rat RPE. This receptor may not be involved in normal OS phagocytic recognition, but may function in the trafficking of lysosomal enzymes by RPE cells.