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Ouafa Ait-Hmyed, Marie-Paule Felder-Schmittbuhl, David Hicks; Circadian Clock Gene Knockout Mice Display Decreased Photoreceptor Phagocytic Turnover. Invest. Ophthalmol. Vis. Sci. 2011;52(14):917.
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The retina exhibits numerous physiological processes regulated by circadian clocks. The present study aimed to see whether specific circadian clock gene knockout mice manifest detectable retinal phenotypes.
Wild type C57Bl6, Per1/Per2 double KO or rev-erbα KO mice were maintained in standard 12 hr light/12 hr dark (L/D) cycles with ad libitum access to food and water. Young adults were examined by ophthalmoscopic exploration, scotopic and photopic electroretinography (ERG) measurements, standard histology, immunohistochemistry and gene expression analysis by qPCR. In one experimental series, mice were killed every 4 hr (n=4 per time point) throughout a 24 hr L/D cycle as well as constant darkness (DD). Their retinas were examined for the presence and number of phagosomes using a standardised immunohistochemical assay.
Fundus examination by scanning laser ophthalmoscopy (SLO) did not reveal any obvious differences between control and mutant mice. There were also no differences between wild type and mutant mice in terms of ERG recordings, or of retinal structure (cell layer thickness) or specific cell type markers [using a battery of antibodies against rod (rhodopsin, rod transducin) or cone (short- and medium/long-wavelength opsins, cone transducin, cone arrestin) photoreceptors]. However, rev-erbα -/- mice displayed increased levels and modified rhythmic expression of several clock genes, and both Per1/Per2 -/- and rev-erbα -/- exhibited a roughly 50% reduction in phagocytic turnover.
The absence of given circadian clock genes does not have an overt effect on retinal structure, phenotypic expression or visual responses, but there is a significant decrease in photoreceptor phagocytosis. This is the first time specific clock genes have been identified as playing a role in this process.
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