Core circadian clock genes Per1 and Per2 regulate the rhythm in photoreceptor outer segment phagocytosis.
Animals
Circadian Clocks
/ genetics
Circadian Rhythm
/ genetics
Female
Male
Mice
Mice, Inbred C57BL
Period Circadian Proteins
/ genetics
Phagocytosis
/ genetics
Photoreceptor Cells
/ physiology
Photoreceptor Cells, Vertebrate
/ physiology
Retina
/ physiology
Retinal Pigment Epithelium
/ physiology
Transcription, Genetic
/ genetics
circadian rhythm
clock gene
phagocytosis
photoreceptor
photoreceptor outer segment
retinal pigment epithelium
Journal
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
ISSN: 1530-6860
Titre abrégé: FASEB J
Pays: United States
ID NLM: 8804484
Informations de publication
Date de publication:
07 2021
07 2021
Historique:
revised:
13
05
2021
received:
17
02
2021
accepted:
24
05
2021
entrez:
23
6
2021
pubmed:
24
6
2021
medline:
17
7
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 34160105
doi: 10.1096/fj.202100293RR
doi:
Substances chimiques
Per1 protein, mouse
0
Per2 protein, mouse
0
Period Circadian Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e21722Informations de copyright
© 2021 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.
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