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Douglas McMahon; Retinal circadian clocks: Organization and relationship to health and disease. Invest. Ophthalmol. Vis. Sci. 2018;59(9):1584. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Presentation Description :
The vertebrate retina is both a sensory organ and a 24-hour biological clock. Our vision is different at different times of day because our retina works differently at different times of day. These rhythms in visual function are not just responses to the daily light-dark cycle, but are in fact the overt expression of the endogenous, self-sustained circadian clock in the retina that drives many rhythms in retinal physiology and metabolism. The retina contains a complete circadian clock system – clock genes that generate 24 hour rhythms, an input pathway by which light synchronizes the cycling of the retinal clock to the environmental light/dark cycle, and neurochemical output pathways that transmit the clock’s influence through-out the retina and into the rest of the brain. The retinal circadian clock drives rhythms in retinal gene expression, synaptic communication and metabolism that globally shape retinal function according to time day. Here we will discuss the molecular, cellular and neurochemical organization of the retinal circadian clock, and consider some of its impacts on health and disease. While the essentials of retinal circadian organization are becoming increasingly clear, fundamental questions persist regarding how the retinal circadian clock may be shaped during development and what are the dimensions in which the retinal circadian clock may impact retinal disease or serve as a biomarker for neurodevelopmental pertubations in the nervous system. Recent results from our laboratory point to early light experience as a critical factor in organizing the nascent retinal clock and dopamine system. In addition we have found that the retinal clock gene network is a key regulator of retinal neovascularization – a fundamental pathological component of several blinding diseases. Finally, we have demonstrated that read-out of the dopaminergic tone of the retina can be performed non-invasively with the ERG, and in a mouse model of ADHD that harbors a specific mutation in the dopamine transported (DAT), the ERG can be used as a non-invasive assay of altered neural dopamine signaling that reflects parallel alterations in central dopamine. This raises the possibility of using retainl circadian dopamine signaling as a non-invasive biomarker for ADHD diagnosis.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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