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• W2977921024 abstract "Abstract Purpose A burst in phagocytosis of spent photoreceptor outer fragments by retinal pigment epithelium (RPE) is a rhythmic process occurring 1-2 hours after the onset of light. This phenomenon is considered crucial for the health of the photoreceptors and RPE. We have recently reported that dopamine, via dopamine 2 receptor (D 2 R), shifts the circadian rhythm in the RPE. Methods Here, we first investigated the impact of the removal of D 2 R on the daily peak of phagocytosis by RPE and then we analyzed the function and morphology of retina and RPE in the absence of D 2 R. Results D 2 R KO mice do not show a daily burst of phagocytic activity after the onset of light. Also, in contrast to control, phosphorylation of FAK did not increase significantly in KO mice at ZT1. RNA sequencing revealed a total of 394 differentially expressed genes (DEGs) between ZT23 and ZT1 in the control mice, whereas in D 2 R KO mice, we detected 1054 DEGs. Pathway analysis of the gene expression data implicated integrin signaling to be one of the upregulated pathways in control but not in D 2 R KO mice. No difference in retinal thickness, visual function, or morphology of RPE cells was observed between WT and D 2 R KO mice at the age of 3 and 12 months. Conclusions Our data suggest that removal of D 2 R prevents the burst in phagocytosis and a related increase in the phosphorylation of FAK after light onset. The pathway analysis points towards a putative role of D 2 R in controlling integrin signaling, which is known to play an important role in the control of the daily burst of phagocytosis by the RPE. Our data also indicate that the absence in the burst of phagocytic activity in the early morning does not produce any apparent deleterious effect on the retina or RPE up to one year of age." @default.
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• W2977921024 date "2019-10-02" @default.
• W2977921024 modified "2023-10-03" @default.
• W2977921024 title "Dopamine 2 receptor signaling controls the daily burst in phagocytic activity in the mouse retinal pigment epithelium" @default.
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• W2977921024 doi "https://doi.org/10.1101/789917" @default.
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