Retinal circadian clocks and non-visual photoreceptors: light input to the circadian system.
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1
INSERM, Chronobiology, France
The mammalian retina contains an endogenous pacemaker that regulates retinal physiology and adjusts daily the temporal phase of the central circadian timing system with environmental time. This entrainment process involves rods, cones and melanopsin-expressing retinal ganglion cells. In contrast with non mammalian retinas, in which the clock has been identified in photoreceptors, the location of the retinal circadian clock in mammals is still controversial. In addition, the impact of specific photoreceptor degeneration on the molecular machinery of the endogenous retinal clock is unknown.
The experimental strategy is based on the isolation of the retina in two separate compartments: inner (inner nuclear and ganglion cell layers) and outer (cones and rods) using laser microdissection and real time RT-PCR. We investigate clock (mPer1-2-3, mClock, mBmal1, mCry1-2, mReverb) and clock-controlled gene (mDbp, mE4bp4) expression in these two retinal compartments during the 24 hr cycle at six circadian times in the wild-type mouse. We next evaluated the impact of the absence of melanopsin on the endogenous functioning of the retinal clock by using Opn4-/- transgenic mouse model.
We find that 1) all core clock genes are expressed in both inner and outer regions of the wild-type retina. All these genes present a significant circadian rhythm (excepting Per3) in the photoreceptor layer whereas in the inner retina, only Per1-2, Clock, Rorb are rhythmic. For all genes significantly cycling in both inner and outer compartments, their expressions are not in phase suggesting that the master clock is localized in photoreceptor cells 2) The absence of melanopsin leads to a dysfunction of the clock mechanism mostly in the outer retina, characterized by a loss of circadian clock gene expression. Because circadian organization is widespread in the retina and controls fundamental pathways, disruption of circadian organization in the retina could potentially have a major impact on retinal functions and on SCN functioning.
Support: RETINA-France, CMIRA
Keywords:
Retina,
Clock genes,
Melanopsin,
Circadian Rhythm,
Photoreceptor Cells
Conference:
4th Conference of the Mediterrarnean Neuroscience Society, Istanbul, Türkiye, 30 Sep - 3 Oct, 2012.
Presentation Type:
Symposium
Topic:
Abstracts
Citation:
Dkhissi-Benyahya
O
(2013). Retinal circadian clocks and non-visual photoreceptors: light input to the circadian system..
Conference Abstract:
4th Conference of the Mediterrarnean Neuroscience Society.
doi: 10.3389/conf.fnhum.2013.210.00024
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Received:
27 Jan 2013;
Published Online:
11 Apr 2013.
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Correspondence:
Dr. Ouria Dkhissi-Benyahya, INSERM, Chronobiology, Bron, 69500, France, ouria.benyahya@inserm.fr