Circadian Regulation of Retinal Pigment Epithelium Function

The retinal pigment epithelium (RPE) is a single layer of cells located between the choriocapillaris vessels and the light-sensitive photoreceptors in the outer retina. The RPE performs physiological processes necessary for the maintenance and support of photoreceptors and visual function. Among the many functions performed by the RPE, the timing of the peak in phagocytic activity by the RPE of the photoreceptor outer segments that occurs 1-2 h. after the onset of light has captured the interest of many investigators and has thus been intensively studied. Several studies have shown that this burst in phagocytic activity by the RPE is under circadian control and is present in nocturnal and diurnal species and rod and cone photoreceptors. Previous investigations have demonstrated that a functional circadian clock exists within multiple retinal cell types and RPE cells. However, the anatomical location of the circadian controlling this activity is not clear. Experimental evidence indicates that the circadian clock, melatonin, dopamine, and integrin signaling play a key role in controlling this rhythm. A series of very recent studies report that the circadian clock in the RPE controls the daily peak in phagocytic activity. However, the loss of the burst in phagocytic activity after light onset does not result in photoreceptor or RPE deterioration during aging. In the current review, we summarized the current knowledge on the mechanism controlling this phenomenon and the physiological role of this peak.