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Coralie GIANESINI, Delphine Hennequin, Daniel Clesse, Gianluca Tosini, David Hicks, Virginie Laurent; Novel regulation of melatonin synthesis by cones and ganglion cells in the retina of a diurnal rodent Arvicanthis ansorgei. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2250.
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© ARVO (1962-2015); The Authors (2016-present)
The “zeitgeber” hormone melatonin is produced in the neural retina, where it can exert local effects on neuronal electric activity (Sengupta et al., 2011), photoreceptor phagocytosis (Besharse et al., 1983) or light sensitivity (Baba et al., 2013). However knowledge about its regulation remains fragmented especially in mammals. In this study, we proposed to accurately characterize melatonin synthesis by studying temporal and spatial localization of the penultimate and last enzymes of the melatonin synthesis pathway: respectively Arylalkylamine N-acetyltransferase (AA-NAT) and Hydroxyindole-O-methytransferase (HIOMT).
The animal model chosen for this study was Arvicanthis ansorgei, a diurnal rodent whose retina resembles to the central human retina, rich in cones photoreceptors (33% against 2-4% in rat and mouse (Bobu et al., 2006)). Cones are essential for acute and color vision and are thought to be involved in the synthesis of melatonin (Niki et al., 1998). In this study retinas of adult Arvicanthis ansorgei were processed for in situ hybridization and immunohistochemistry in order to study spatial localization of AA-NAT and HIOMT. Western blotting, enzymatic assays, HPLC and melatonin assay were performed to analyze temporal synthesis of AA-NAT, HIOMT, melatonin and dopamine.
We report that AA-NAT expression and activity span over the 24 hours, albeit a tendency to increase during the night. HIOMT activity and melatonin secretion are both constitutive and with a low level. Dopamine, a neurotransmitter known to interact with melatonin presents a rhythmic expression (p < 0.05). AA-NAT and HIOMT are localized in cone photoreceptors as well as ganglion cells layers. Melatonin receptors MT1 are distributed in photoreceptors, inner nuclear layer and ganglion cells layers.
These data demonstrate for the first time that melatonin is produced in two different nuclear layers in mammals: photoreceptors (cones) and ganglion cells layers. This hormone potentially exerts an effect on all cell layers in the retina. The presence of melatonin as well as AA-NAT and HIOMT over the 24 hours while dopamine classically rises at the beginning of the day, suggested a different regulation of melatonin synthesis in diurnal mammalian retina compared with the accepted mechanism in the rat retina or in the pineal gland.
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