Rod Outer Segment Renewal Research Articles

Kinetics of rod outer segment renewal in the developing mouse retina.

The kinetics of rod outer segment renewal in the developing retina have been investigated in C57BL/6J mice. Litters of mice were injected with [(3)H]amino acids at various ages and killed at progressively later time intervals. Plastic 1.5 microm sections of retina were studied by light microscope autoradiography. The rate of outer segment disk synthesis, as judged by labeled disk displacement away from the site of synthesis, is slightly greater than the adult level at 11-13 days of age; it rises to more than 1.6 times the adult rate between days 13 and 17, after which it falls to the adult level at 21-25 days. The rate of disk disposal, as measured by labeled disk movement toward the site of disposal, is less than 15% of the adult level at 11-13 days of age; it rises sharply to almost 70% of the adult level by days 13-15 and then more gradually approaches the adult rate. The net difference in rates of synthesis and disposal accounts for the rapid elongation of rod outer segments in the mouse between days 11 and 17 and the subsequent, more gradual elongation to the adult equilibrium length reached between days 19 and 25. The changing rate of outer segment disk synthesis characterizes the late stages of cytodifferentiation of the rod photoreceptor cells.

THE RENEWAL OF ROD AND CONE OUTER SEGMENTS IN THE RHESUS MONKEY

The renewal of retinal rod and cone outer segments has been studied by radioautography in rhesus monkeys examined 2 and 4 days after injection of leucine-(3)H. The cell outer segment consists of a stack of photosensitive, membranous discs. In both rods and cones some of the newly formed (radioactive) protein became distributed throughout the outer segment. Furthermore, in rods (but not in cones), there was a transverse band of concentrated radioactive protein slightly above the outer segment base 2 days after injection. This was due to the formation of new discs, into which labeled protein had been incorporated. At 4 days, these radioactive discs were located farther from the outer segment base. Repeated assembly of new discs had displaced them away from the basal assembly site and along the outer segment. Measurements of the displacement rate indicated that each retinal rod produces 80-90 discs per day, and that the entire complement of outer segment discs is replaced every 9-13 days. To compensate for the continual formation of new discs, groups of old discs are intermittently shed from the apical end of the cell and phagocytized by the pigment epithelium. Each pigment epithelial cell engulfs and destroys about 2000-4000 rod outer segment discs daily. The similarity between visual cells in the rhesus monkey and those in man suggests that the same renewal processes occur in the human retina.

Participation of the retinal pigment epithelium in the rod outer segment renewal process.

The disposal phase of the retinal rod outer segment renewal process has been studied by radioautography in adult frogs injected with tritiated amino acids. Shortly after injection, newly formed radioactive protein is incorporated into disc membranes which are assembled at the base of the rod outer segment. During the following 2 months, these labeled discs are progressively displaced along the outer segment owing to the repeated formation of newer discs. When the labeled membranes reach the end of the outer segment, they are detached from it. They subsequently may be identified in inclusion bodies within the pigment epithelium by virtue of their content of radioactivity. These inclusions have been termed phagosomes. Disc membrane formation is a continuous process, but the detachment of groups of discs occurs intermittently. The detached outer segment fragments become deformed, compacted, undergo chemical changes, and are displaced within the pigment epithelium. Ultimately, the material contained in the phagosomes is eliminated from the cell. In this manner the pigment epithelium participates actively in the disposal phase of the rod outer segment renewal process.