Dopaminergic and GABAergic amacrine cells are direct targets of melatonin: Immunocytochemical study of mt₁ melatonin receptor in guinea pig retina

Abstract

Distribution of the mt1 melatonin receptor in the guinea pig retina was immunocytochemically investigated using peptide-specific anti-mt1 receptor antibody. Western blots of the guinea pig retina showed a single band at approximately 37 kilodalton (kD) immunoreactive to the anti-mt1 antibody. The most intense immunoreactivity for the mt1 receptor was detected in the cell bodies of ganglion cells. Their dendrites and axons were also immunolabeled. Subpopulations of amacrine cells, the inner plexiform layer, and the outer plexiform layer also exhibited moderate to weak immunolabeling. The mt1-positive amacrine cells were located either at the vitreal border of the inner nuclear layer or displaced in the ganglion cell layer. Double immunolabeling using antibodies to the mt1 receptor and tyrosine hydroxylase revealed that the majority of dopaminergic amacrine cells showed mt1 immunoreactivity. Almost all the ICA type dopaminergic cells were mt1 positive while the 2CA type cells less frequently exhibited mt1 immunoreaction. By double immunolabeling for the mt1 receptor and GABA, more than 50% of the mt1-immunoreactive amacrine cells were shown to be GABAergic neurons. Approximately one-third of the GABAergic amacrine cells were immunolabeled for the mt1 receptor. The present results demonstrate expression of the mt1 receptor in diverse neuronal cell types in the guinea pig retina and provide the first evidence for the direct effect of melatonin on dopaminergic and GABAergic amacrine cells via the mt1 receptor.

Melatonin modulates visual function and cell viability in the mouse retina via the MT1 melatonin receptor

“…1). The distribution of MT1 mRNA that we have observed is consistent with data reported in the literature in other mammalian species (12,13).…”

“…Melatonin receptors are expressed by several retinal cell types, including the photoreceptors (12,13), suggesting that melatonin receptors may be involved in the regulation of photoreceptor physiology. Indeed, previous studies have reported that melatonin influences the membrane conductance of dark adapted frog photoreceptors (14), acts directly on the rod photoreceptors to increase dark adaptation (15), and potentiates rod signals to ON type bipolar cells in fish retina (16).…”

Orexins and Their Receptors in the Human Retina

“…These cells are also susceptible to the regulatory action of an important circadian modulatory hormone, melatonin [24,31] . Dopaminergic and GABAergic output of the amacrine cells is directly regulated by melatonin [31] .…”

“…Dopaminergic and GABAergic output of the amacrine cells is directly regulated by melatonin [31] . Since orexin-A-and orexin-B-positive fi bers [9] and OX-R1 expression [16] have been localized in the SCN, orexins may be involved in the retinohypothalamic tract from the amacrine and ganglion cells projecting to the SCN.…”

Circadian Rhythms of Dopamine and Dihydroxyphenyl Acetic Acid in the Mouse Striatum: Effects of Pinealectomy and of Melatonin Treatment

“…Besides, aMT increases GABA content and regulates the circadian rhythm of its receptors in the CNS [13, 14], and dopaminergic and GABAergic cells are target for aMT [39]. DA exerts its striatal effect acting on both D 1 and D 2 receptors mainly located on GABAergic neurons into the striatum.…”