Stefanie Kunst1, Tanja Wolloscheck2, Debra K Kelleher2, Uwe Wolfrum3, S Anna Sargsyan4, P Michael Iuvone4, Kenkichi Baba5, Gianluca Tosini5, Rainer Spessert2. 1. Institute of Functional and Clinical Anatomy University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany 2Department of Cell and Matrix Biology, Institute of Zoology, Johannes Gutenberg University, Mainz, Germany. 2. Institute of Functional and Clinical Anatomy University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany. 3. Department of Cell and Matrix Biology, Institute of Zoology, Johannes Gutenberg University, Mainz, Germany. 4. Departments of Ophthalmology and Pharmacology, Emory University School of Medicine, Atlanta, Georgia, United States. 5. Neuroscience Institute and Department of Pharmacology and Toxicology, Morehouse School of Medicine, Atlanta, Georgia, United States.
Abstract
PURPOSE: The neurohormones melatonin and dopamine mediate clock-dependent/circadian regulation of inner retinal neurons and photoreceptor cells and in this way promote their functional adaptation to time of day and their survival. To fulfill this function they act on melatonin receptor type 1 (MT1 receptors) and dopamine D4 receptors (D4 receptors), respectively. The aim of the present study was to screen transcriptional regulators important for retinal physiology and/or pathology (Dbp, Egr-1, Fos, Nr1d1, Nr2e3, Nr4a1, Pgc-1α, Rorβ) for circadian regulation and dependence on melatonin signaling/MT1 receptors or dopamine signaling/D4 receptors. METHODS: This was done by gene profiling using quantitative polymerase chain reaction in mice deficient in MT1 or D4 receptors. RESULTS: The data obtained determined Pgc-1α and Nr4a1 as transcriptional targets of circadian melatonin and dopamine signaling, respectively. CONCLUSIONS: The results suggest that Pgc-1α and Nr4a1 represent candidate genes for linking circadian neurohormone release with functional adaptation and healthiness of retina and photoreceptor cells.
PURPOSE: The neurohormones melatonin and dopamine mediate clock-dependent/circadian regulation of inner retinal neurons and photoreceptor cells and in this way promote their functional adaptation to time of day and their survival. To fulfill this function they act on melatonin receptor type 1 (MT1 receptors) and dopamine D4 receptors (D4 receptors), respectively. The aim of the present study was to screen transcriptional regulators important for retinal physiology and/or pathology (Dbp, Egr-1, Fos, Nr1d1, Nr2e3, Nr4a1, Pgc-1α, Rorβ) for circadian regulation and dependence on melatonin signaling/MT1 receptors or dopamine signaling/D4 receptors. METHODS: This was done by gene profiling using quantitative polymerase chain reaction in mice deficient in MT1 or D4 receptors. RESULTS: The data obtained determined Pgc-1α and Nr4a1 as transcriptional targets of circadian melatonin and dopamine signaling, respectively. CONCLUSIONS: The results suggest that Pgc-1α and Nr4a1 represent candidate genes for linking circadian neurohormone release with functional adaptation and healthiness of retina and photoreceptor cells.
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