scholarly journals Dopamine 2 receptor signaling controls the daily burst in phagocytic activity in the mouse retinal pigment epithelium

2019 ◽  
Author(s):  
Varunika Goyal ◽  
Christopher DeVera ◽  
Virginie Laurent ◽  
Jana Sellers ◽  
Micah A. Chrenek ◽  
...  
Keyword(s):  
Retinal Pigment Epithelium ◽  
Pathway Analysis ◽  
Phagocytic Activity ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Early Morning ◽  
Integrin Signaling ◽  
One Year ◽  
Dopamine 2 Receptor ◽  
The Impact

AbstractPurposeA 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 (D2R), shifts the circadian rhythm in the RPE.MethodsHere, we first investigated the impact of the removal of D2R on the daily peak of phagocytosis by RPE and then we analyzed the function and morphology of retina and RPE in the absence of D2R.ResultsD2R 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 D2R 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 D2R KO mice. No difference in retinal thickness, visual function, or morphology of RPE cells was observed between WT and D2R KO mice at the age of 3 and 12 months.ConclusionsOur data suggest that removal of D2R 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 D2R 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.

scholarly journals Dopamine 2 Receptor Signaling Controls the Daily Burst in Phagocytic Activity in the Mouse Retinal Pigment Epithelium

2020 ◽  
Vol 61 (5) ◽  
pp. 10 ◽  
Author(s):  
Varunika Goyal ◽  
Christopher DeVera ◽  
Virginie Laurent ◽  
Jana Sellers ◽  
Micah A. Chrenek ◽  
...  
Keyword(s):  
Retinal Pigment Epithelium ◽  
Phagocytic Activity ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Receptor Signaling ◽  
Dopamine 2 Receptor

scholarly journals Regulation of phagolysosomal activity by miR-204 critically influences structure and function of retinal pigment epithelium/retina

2019 ◽  
Vol 28 (20) ◽  
pp. 3355-3368 ◽  
Author(s):  
Congxiao Zhang ◽  
Kiyoharu J Miyagishima ◽  
Lijin Dong ◽  
Aaron Rising ◽  
Malika Nimmagadda ◽  
...  
Keyword(s):  
Retinal Pigment Epithelium ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Primary Cultures ◽  
Structure And Function ◽  
Apical Surface ◽  
Altered Expression ◽  
And Function ◽  
The Impact

Abstract MicroRNA-204 (miR-204) is expressed in pulmonary, renal, mammary and eye tissue, and its reduction can result in multiple diseases including cancer. We first generated miR-204−/− mice to study the impact of miR-204 loss on retinal and retinal pigment epithelium (RPE) structure and function. The RPE is fundamentally important for maintaining the health and integrity of the retinal photoreceptors. miR-204−/− eyes evidenced areas of hyper-autofluorescence and defective photoreceptor digestion, along with increased microglia migration to the RPE. Migratory Iba1+ microglial cells were localized to the RPE apical surface where they participated in the phagocytosis of photoreceptor outer segments (POSs) and contributed to a persistent build-up of rhodopsin. These structural, molecular and cellular outcomes were accompanied by decreased light-evoked electrical responses from the retina and RPE. In parallel experiments, we suppressed miR-204 expression in primary cultures of human RPE using anti-miR-204. In vitro suppression of miR-204 in human RPE similarly showed abnormal POS clearance and altered expression of autophagy-related proteins and Rab22a, a regulator of endosome maturation. Together, these in vitro and in vivo experiments suggest that the normally high levels of miR-204 in RPE can mitigate disease onset by preventing generation of oxidative stress and inflammation originating from intracellular accumulation of undigested photoreactive POS lipids. More generally, these results implicate RPE miR-204-mediated regulation of autophagy and endolysosomal interaction as a critical determinant of normal RPE/retina structure and function.

scholarly journals Melatonin signaling affects the timing in the daily rhythm of phagocytic activity by the retinal pigment epithelium

2017 ◽  
Vol 165 ◽  
pp. 90-95 ◽  
Author(s):  
Virgine Laurent ◽  
Anamika Sengupta ◽  
Aída Sánchez-Bretaño ◽  
David Hicks ◽  
Gianluca Tosini
Keyword(s):  
Retinal Pigment Epithelium ◽  
Phagocytic Activity ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Daily Rhythm

scholarly journals Comparative gene expression study and pathway analysis of the human iris- and the retinal pigment epithelium

PLoS ONE ◽  
2017 ◽  
Vol 12 (8) ◽  
pp. e0182983 ◽  
Author(s):  
Anna Bennis ◽  
Jacoline B. ten Brink ◽  
Perry D. Moerland ◽  
Vivi M. Heine ◽  
Arthur A. Bergen
Keyword(s):  
Gene Expression ◽  
Retinal Pigment Epithelium ◽  
Pathway Analysis ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Gene Expression Study ◽  
Expression Study ◽  
Human Iris

scholarly journals The Impact of miRNAs in Health and Disease of Retinal Pigment Epithelium

2021 ◽  
Vol 8 ◽  
Author(s):  
Daniela Intartaglia ◽  
Giuliana Giamundo ◽  
Ivan Conte
Keyword(s):  
Retinal Pigment Epithelium ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Fine Tuning ◽  
Molecular Networks ◽  
Therapeutic Approaches ◽  
Pathological Conditions ◽  
Health And Disease ◽  
Non Coding Rnas ◽  
The Impact

MicroRNAs (miRNAs), a class of non-coding RNAs, are essential key players in the control of biological processes in both physiological and pathological conditions. miRNAs play important roles in fine tuning the expression of many genes, which often have roles in common molecular networks. miRNA dysregulation thus renders cells vulnerable to aberrant fluctuations in genes, resulting in degenerative diseases. The retinal pigment epithelium (RPE) is a monolayer of polarized pigmented epithelial cells that resides between the light-sensitive photoreceptors (PR) and the choriocapillaris. The demanding physiological functions of RPE cells require precise gene regulation for the maintenance of retinal homeostasis under stress conditions and the preservation of vision. Thus far, our understanding of how miRNAs function in the homeostasis and maintenance of the RPE has been poorly addressed, and advancing our knowledge is central to harnessing their potential as therapeutic agents to counteract visual impairment. This review focuses on the emerging roles of miRNAs in the function and health of the RPE and on the future exploration of miRNA-based therapeutic approaches to counteract blinding diseases.

scholarly journals THE CIRCADIAN CLOCK IN THE RETINAL PIGMENT EPITHELIUM CONTROLS THE DIURNAL RHYTHM OF PHAGOCYTIC ACTIVITY

2020 ◽  
Author(s):  
Christopher DeVera ◽  
Jendayi Dixon ◽  
Micah A. Chrenek ◽  
Kenkichi Baba ◽  
P. Michael Iuvone ◽  
...  
Keyword(s):  
Retinal Pigment Epithelium ◽  
Circadian Clock ◽  
Phagocytic Activity ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Optomotor Response ◽  
Rpe Cells ◽  
Photoreceptor Outer Segments ◽  
Outer Segments ◽  
Old Mice

AbstractThe 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.

scholarly journals The Impact of cHS4 Insulators on DNA Transposon Vector Mobilization and Silencing in Retinal Pigment Epithelium Cells

PLoS ONE ◽  
2012 ◽  
Vol 7 (10) ◽  
pp. e48421 ◽  
Author(s):  
Nynne Sharma ◽  
Anne Kruse Hollensen ◽  
Rasmus O. Bak ◽  
Nicklas Heine Staunstrup ◽  
Lisbeth Dahl Schrøder ◽  
...  
Keyword(s):  
Retinal Pigment Epithelium ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Dna Transposon ◽  
Retinal Pigment Epithelium Cells ◽  
The Impact ◽  
Epithelium Cells

scholarly journals Comparison of Progression Rate of Retinal Pigment Epithelium Loss in Patients with Neovascular Age-Related Macular Degeneration Treated with Ranibizumab and Aflibercept

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Juliana Wons ◽  
Magdalena A. Wirth ◽  
Nicole Graf ◽  
Matthias D. Becker ◽  
Stephan Michels
Keyword(s):  
Retinal Pigment Epithelium ◽  
Macular Degeneration ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Progression Rate ◽  
Intravitreal Ranibizumab ◽  
Age Related ◽  
Significant Difference ◽  
One Year

Purpose. Retinal pigment epithelium (RPE) loss in neovascular age-related macular degeneration (nAMD) seem to have a linear progression but might be influenced by the treatment. The purpose of the study is the comparison of RPE loss over three years in patients treated with intravitreal ranibizumab to patients who were switched to aflibercept. Methods. A retrospective analysis with 96 eyes switched to aflibercept was conducted. The progression rate of RPE loss was evaluated in patients who showed atrophy one year prior to switch (n=17) or on switch date (n=19). The RPE loss was evaluated by spectral domain optical coherence tomography (SD-OCT). Further, 22 eyes from patients treated with ranibizumab were compared. Results. The median yearly progression of RPE loss after square root transformation showed no significant difference in the year prior to switch compared to the year after switch (p=0.854). In patients who received only ranibizumab, the median yearly progression of RPE loss was 0.15 mm/y, for aflibercept patients, 0.13 mm/y. This difference was not statistically significant (p=0.172). Conclusions. There seems to be a linear progression rate of RPE loss in patients treated with ranibizumab as well as in patients with aflibercept. No significant increase of progression rate was found after switch to aflibercept.

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