6533b7d7fe1ef96bd12683a5

RESEARCH PRODUCT

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subject

0301 basic medicinemedicine.medical_specialtyRetinaMultidisciplinarygenetic structuresG proteinDopaminergicBiologyeye diseasesPinealocyteCell biology03 medical and health sciencesPineal gland030104 developmental biology0302 clinical medicinemedicine.anatomical_structureEndocrinologyDopamineInternal medicinemedicinesense organsCircadian rhythmSignal transduction030217 neurology & neurosurgerymedicine.drug

description

The mammalian retina harbors a circadian clockwork that regulates vision and promotes healthiness of retinal neurons, mainly through directing the rhythmic release of the neurohormones dopamine-acting on dopamine D4 receptors-and melatonin-acting on MT1 and MT2 receptors. The gene Gnaz-a unique Gi/o subfamily member-was seen in the present study to be expressed in photoreceptors where its protein product Gαz shows a daily rhythm in its subcellular localization. Apart from subcellular localization, Gnaz displays a daily rhythm in expression-with peak values at night-in preparations of the whole retina, microdissected photoreceptors and photoreceptor-related pinealocytes. In retina, Gnaz rhythmicity was observed to persist under constant darkness and to be abolished in retina deficient for Clock or dopamine D4 receptors. Furthermore, circadian regulation of Gnaz was disturbed in the db/db mouse, a model of diabetic retinopathy. The data of the present study suggest that Gnaz links the circadian clockwork-via dopamine acting on D4 receptors-to G protein-mediated signaling in intact but not diabetic retina.