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C. Ribelayga, S. C. Mangel; The Circadian Clock in the Mammalian Retina Regulates Dopamine Release and Rod-Cone Coupling by Producing Rhythmic Melatonin Release. Invest. Ophthalmol. Vis. Sci. 2010;51(13):2045.
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Although mammalian retinas contain a circadian (24-hr) clock that produces more melatonin at night than in the day and melatonin inhibits dopamine release, it is not known whether the increased level of dopamine release during the day is due to a clock located within or outside of the retina and whether it results from the inactivity of melatonin receptors during the day.
Isolated mouse neural retinas from the CBA/CaJ strain, which rhythmically synthesizes melatonin, and the C57BL/6J strain, which does not synthesize melatonin (Roseboom et al., 1998), were cultured for up to 3 days in constant darkness. The culture medium was changed every 4 h and dopamine contained in the medium was quantified using reversed-phase HPLC with electrochemical detection. The extent of gap junctional coupling between photoreceptors was assessed by neurobiotin diffusion using a cut-loading technique.
In CBA/CaJ, but not in C57BL/6J, mouse retinas, the amount of dopamine in the medium exhibited a circadian rhythm with a period of ~ 24 h. The highest levels of dopamine were observed during the subjective day and the lowest during the subjective night. Photoreceptor cells in CBA/CaJ retinas displayed considerable tracer coupling during the subjective night under control conditions and during the day in the presence of the D2 receptor antagonist spiperone (10 µM), but neurobiotin was restricted to the edge of the cut during the subjective day. In contrast, in C57BL/6J mouse retinas neurobiotin was restricted to the edge of the cut during both the subjective day and night, but was observed as far as 60 µm from the cut during the subjective day in the presence of spiperone (10 µM).
These results indicate that the circadian clock in the mammalian retina regulates dopamine release and modulates rod-cone tracer coupling via dopamine D2 receptors. The findings also suggest that the circadian rhythm in melatonin synthesis and release generates the anti-phase rhythm of dopamine release and the D2 receptor-mediated day/night difference in rod-cone coupling.
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