Differential day-night expression of tight junction components in murine retinal pigment epithelium

Louer, Elja; Günzel, Dorothee; Rosenthal, Rita; Carmone, Claudia; Yi, Guoqiang; Stunnenberg, Henk; Hollander, Anneke I. den; Deen, Peter M.T.

doi:10.1016/j.exer.2020.107985

Cited by 16 publications

(14 citation statements)

References 56 publications

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“…Many studies have shown that 10-20% of the mouse transcriptome is under circadian clock control in many tissues/organs (Hughes et al, 2017), including the RPE (DeVera and Tosini, 2020;Louer et al, 2020a). Not surprisingly, the transcriptional processes under circadian regulation in the RPE include many of the pathways known to be involved in the regulation of phagocytic activity and metabolism, such as actin cytoskeleton remodeling (Bulloj et al, 2013;Louer et al, 2020a), integrin signaling (Goyal et al, 2020a;Nandrot et al, 2004), cAMP signaling (Mustafi et al, 2013), protein phosphorylation (Lakkaraju et al, 2020) and mitochondrial electron transport chain (DeVera and Tosini, 2020;Louer et al, 2020b). Hence, it is quite surprising that the removal of a functional circadian clock from the RPE did not induce any negative phenotype.…”

Section: Discussionmentioning

confidence: 99%

The Circadian Clock in the Retinal Pigment Epithelium Controls the Diurnal Rhythm of Phagocytic Activity

DeVera

Dixon

Chrenek

et al. 2020

Preprint

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The diurnal peak of phagocytosis by the retinal pigment epithelium (RPE) of photoreceptor outer segments (POS) is under circadian control, and it is believed that this process involves interactions from both the retina and RPE. Previous studies have demonstrated that a functional circadian clock exists within multiple retinal cell types and RPE cells. Thereby, the aim of the current study was to determine whether the circadian clock in the retina and or RPE controls the diurnal phagocytic peak of photoreceptor outer segments and whether selective disruption of the circadian clock in the RPE would affect RPE cells function and the viability during aging. To that aim, we first generated and validated an RPE tissue-specific KO of the essential clock gene, Bmal1, and then we determined the daily rhythm in phagocytic activity by the RPE in mice lacking a functional circadian clock in the retina or RPE. Then using electroretinography, spectral domain-optical coherence tomography, and optomotor response measurements of visual function we determined the effect of Bmal1 removal in young (6-month old) and old (18-month old) mice. RPE morphology and lipofuscin accumulation was also determined in young and old mice. Our data show that the circadian clock in the RPE controls the daily diurnal phagocytic peak of POS. Surprisingly, the lack of a functional RPE circadian clock or the diurnal phagocytic peak does not result in any detectable age-related degenerative phenotype in the retina or RPE. Thus, our results demonstrate that the loss of the circadian clock in the RPE or the lack of the daily peak in phagocytosis of POS does not result in deterioration of photoreceptors or the RPE during aging.

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Section: Discussionmentioning

confidence: 99%

The Circadian Clock in the Retinal Pigment Epithelium Controls the Diurnal Rhythm of Phagocytic Activity

DeVera

Dixon

Chrenek

et al. 2020

Preprint

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“…Also in the HPAI gene expression network, the PARD6G gene (Par-6 Family Cell Polarity Regulator Gamma) was seen to be down-regulated. It is thought to play a role in the formation of epithelial tight junctions [ 43 ]. The expression changes occurring in these genes could help explain the differences in mortality seen between LPAI and HPAI infection in chickens.…”

Section: Discussionmentioning

confidence: 99%

Network Meta-Analysis of Chicken Microarray Data following Avian Influenza Challenge—A Comparison of Highly and Lowly Pathogenic Strains

Pirbaluty

Mehrban

Kadkhodaei

et al. 2022

Genes

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The current bioinformatics study was undertaken to analyze the transcriptome of chicken (Gallus gallus) after influenza A virus challenge. A meta-analysis was carried out to explore the host expression response after challenge with lowly pathogenic avian influenza (LPAI) (H1N1, H2N3, H5N2, H5N3 and H9N2) and with highly pathogenic avian influenza (HPAI) H5N1 strains. To do so, ten microarray datasets obtained from the Gene Expression Omnibus (GEO) database were normalized and meta-analyzed for the LPAI and HPAI host response individually. Different undirected networks were constructed and their metrics determined e.g., degree centrality, closeness centrality, harmonic centrality, subgraph centrality and eigenvector centrality. The results showed that, based on criteria of centrality, the CMTR1, EPSTI1, RNF213, HERC4L, IFIT5 and LY96 genes were the most significant during HPAI challenge, with PARD6G, HMG20A, PEX14, RNF151 and TLK1L having the lowest values. However, for LPAI challenge, ZDHHC9, IMMP2L, COX7C, RBM18, DCTN3, and NDUFB1 genes had the largest values for aforementioned criteria, with GTF3C5, DROSHA, ATRX, RFWD2, MED23 and SEC23B genes having the lowest values. The results of this study can be used as a basis for future development of treatments/preventions of the effects of avian influenza in chicken.

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“…These results suggest that POS phagocytosis is initiated by the RPE. This possibility is, indeed, plausible because the RPE was shown to display sustained rhythms in various models: in vivo, 29,[63][64][65][66] ex vivo, [67][68][69] and in cell culture models. [69][70][71][72][73] Importantly, the phagocytic machinery is rhythmic in these cells.…”

Section: Discussionmentioning

confidence: 99%

Core circadian clock genes Per1 and Per2 regulate the rhythm in photoreceptor outer segment phagocytosis

et al. 2021

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Retinal photoreceptors undergo daily renewal of their distal outer segments, a process indispensable for maintaining retinal health. Photoreceptor outer segment (POS) phagocytosis occurs as a daily peak, roughly about 1 hour after light onset. However, the underlying cellular and molecular mechanisms which initiate this process are still unknown. Here we show that, under constant darkness, mice deficient for core circadian clock genes (Per1 and Per2) lack a daily peak in POS phagocytosis. By qPCR analysis, we found that core clock genes were rhythmic over 24 hours in both WT and Per1, Per2 double mutant whole retinas. More precise transcriptomics analysis of laser capture microdissected WT photoreceptors revealed no differentially expressed genes between time points preceding and during the peak of POS phagocytosis. In contrast, we found that microdissected WT retinal pigment epithelium (RPE) had a number of genes that were differentially expressed at the peak phagocytic time point compared to adjacent ones. We also found a number of differentially expressed genes in Per1, Per2 double mutant RPE compared to WT ones at the peak phagocytic time point. Finally, based on STRING analysis, we found a group of interacting genes that potentially drive POS phagocytosis in the RPE. This potential pathway consists of genes such as: Pacsin1, Syp, Camk2b, and Camk2d among others. Our findings indicate that Per1 and Per2 are necessary clock components for driving POS phagocytosis and suggest that this process is transcriptionally driven by the RPE.

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Differential day-night expression of tight junction components in murine retinal pigment epithelium

Cited by 16 publications

References 56 publications

The Circadian Clock in the Retinal Pigment Epithelium Controls the Diurnal Rhythm of Phagocytic Activity

The Circadian Clock in the Retinal Pigment Epithelium Controls the Diurnal Rhythm of Phagocytic Activity

Network Meta-Analysis of Chicken Microarray Data following Avian Influenza Challenge—A Comparison of Highly and Lowly Pathogenic Strains

Core circadian clock genes Per1 and Per2 regulate the rhythm in photoreceptor outer segment phagocytosis

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