The retinal pigment epithelium (RPE) plays an important role in the maintenance of photoreceptors health and functioning. Previous studies have shown that RPE is also involved in the regulation of the disc shedding, a process that is that is vital for the health of the photoreceptors. This process has been shown to be under circadian control, albeit the mechanisms controlling this circadian rhythm are still poorly understood. Our laboratory has developed a novel preparation in which circadian rhythms in RPE can be easily monitored using the PER2::LUC mouse. Our preliminary data indicate that a circadian rhythm in PER2::LUC bioluminescence can be recorded from cultured RPE and the phase of such a rhythm is different from the phase observed in the retina. Light does phase-shift the circadian rhythm in the RPE, and SCN lesion does not affect the phase of this rhythm. Interestingly, we discovered that Dopamine application can shift the circadian rhythm in the RPE. In this exploratory application, we propose to investigate the role of Dopamine and Dopamine receptors in the regulation of the circadian rhythms in the RPE and the circadian regulation of the RPE transcriptome.

PUBLIC HEALTH RELEVANCE: The retinal pigment epithelium (RPE) plays an important role in the maintenance of photoreceptors health and functioning. Previous studies have shown that RPE is also involved in the regulation of the disc shedding, a process that is that is vital for the health of the photoreceptors. This process has been shown to be under circadian control, albeit the mechanisms controlling this circadian rhythm are still poorly understood. Modern life style has tremendously changed the time at which we expose ourselves to light;hence, it is important to understand how the circadian clock controls the rhythmic event in this organ. Indeed, the national plan for the eye and vision research of the National Eyes Institute states as one of its primary program objective the understanding of the mechanisms controlling the circadian shedding of photoreceptor outer segments and their phagocytosis by the RPE. In this grant application, we propose first to determine the role of DA in the entrainment of PER2::LUC circadian rhythm in the RPE and then to identify genes showing a circadian pattern of expression in RPE. This effort could prove a valuable tool to discovering genes and molecular pathways regulating rhythmic event in the RPE.

R21EY020821

2010-07-01

2013-06-30