![]() ![]() the amplitude of the a- and b-wave of the scotopic ERG) and accumulate more lipofuscin in the RPE with respect to control mice. Moreover, during the aging process, β5 −/− mice also show a decrease in visual function (i.e. 11 – 14 Disruption in the daily peak of RPE phagocytosis impairs retinal and/or RPE functions because mice in which the ανβ5 integrin receptor has been disabled by removing the gene Itgb5, which codes for the β5 subunit of the receptor (β5 −/− mice), fail to show the morning burst of phagocytic activity. 11 – 14 This peak or burst in phagocytosis follows a circadian rhythm as the peak continues to occur even after the animals are kept in complete darkness. Our data also indicate that the absence of the burst of phagocytic activity in the early morning does not produce any apparent deleterious effect on the retina or RPE up to 1 year of age.įurther studies have also shown that the phagocytic activity of the RPE peaks in the morning, shortly after the onset of light (1–2 hours) in many different mammalian species. The pathway analysis points toward a putative role of D 2R 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 suggest that removal of D 2R prevents the burst of phagocytosis and a related increase in the phosphorylation of FAK after light onset. No difference in retinal thickness, visual function, or morphology of RPE cells was observed between wild-type (WT) and D 2R KO mice at the age of 3 and 12 months. Consistent with the gene expression data, phosphorylation of focal adhesion kinase (FAK) did not increase significantly in KO mice at ZT 1. Pathway analysis of the gene expression data implicated integrin signaling to be one of the upregulated pathways in control but not in D 2R KO mice. ![]() RNA sequencing revealed a total of 394 differentially expressed genes (DEGs) between ZT 23 and ZT 1 in the control mice, whereas in D 2R KO mice, we detected 1054 DEGs. Here, we first investigated the impact of the removal of D 2R 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 2R.ĭ 2R knockout (KO) mice do not show a daily burst of phagocytic activity after the onset of light. We have recently reported that dopamine, via dopamine 2 receptor (D 2R), shifts the circadian rhythm in the RPE. This phenomenon is considered crucial for the health of the photoreceptors and RPE. A burst in phagocytosis of spent photoreceptor outer fragments by RPE is a rhythmic process occurring 1 to 2 hours after the onset of light. ![]()
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