Circadian regulation of vertebrate cone photoreceptor function.
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ABSTRACT:
SUBMITTER: Zang J
PROVIDER: S-EPMC8494479 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Here we reveal a novel role for the circadian clock gene Bmal1 and Period2 in regulating the spatial organization of the cone opsins. Deletion of Bmal1 and Per2 have opposing effects on S-opsin expression and patterning of the cone photoreceptors is disrupted in cone specific knockouts of these genes. Using ChIP analysis we show that BMAL1 directly binds to the promoter region of the thyroid activating enzyme type II deiodinase (Dio2).
2017-10-17 | GSE103484 | GEO
Project description:Background: The mammalian retina contains an autonomous circadian clock that controls many physiological functions within this tissue. Our previous studies have indicated that disruption of this circadian clock by removing Bmal1 from the retina affects the visual function, retinal circuitry, and cone photoreceptor viability during aging. In the present study, we employed a mouse-derived cone photoreceptor‒like cell, 661W, to investigate which molecular mechanisms of the circadian clock may modulate cone photoreceptor viability during aging. Methods: Bmal1 knockout (BKO) cells were generated from 661W cells using the CRISPR/Cas9 gene editing tool. Deletion of Bmal1 from 661W was verified by western blot and monitoring Per2-luc bioluminescence circadian rhythms. To investigate the effect of Bmal1 removal on an oxidative stress challenge, cells were treated with hydrogen peroxide (H 2O 2,1 mM) for two hours and then cell viability was assessed. Cells were also cultured and harvested for gene expression analysis and antioxidant assay. Results: Our data indicated that 661W cells contain a functional circadian clock that mediates the response to an oxidative stress challenge in vitro and that such a response is no longer present in the BKO cell. We also hypothesized that the effect was due to the circadian regulation of the intracellular antioxidant defense mechanism. Our results revealed that in 661W cells, the antioxidant defense mechanism showed time dependent variation , whereas in BKO cells, there was an overall reduction in this antioxidant defense mechanism, and it no longer showed time dependent variation. Conclusions: Our work supported the notion that the presence of a functional circadian clock and its ability to modulate the response to an oxidative stress is the underlying mechanism that may protect cones during aging.
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