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Gianluca Tosini, Kenkichi Baba, Susana Contreras-Alcantara; Removals Of Melatonin Receptor Type 2 Abolish The Diurnal Rhythm Of The Dark-adapted Electroretinogram In The Mouse. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5283.
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© ARVO (1962-2015); The Authors (2016-present)
Previous studies have shown that melatonin modulates many retinal functions and our laboratory has recently reported that mice lacking melatonin receptors type 1 (MT1-/-) did not show a diurnal rhythm in the dark-adapted electroretinogram (ERG) responses. Aim of the present study was to investigate the distribution of the melatonin receptor type 2 (MT2) in the retina and the effects that its removal will produce on the diurnal rhythm of the dark-adapted ERG
Melatonin receptor type 2 knock-out mice (MT2-\-) in a C3H/f+/+ background (WT) were generated in our laboratory as described in Contreras-Alcantara et al., (Obesity 18: 1861-1863; 2010). MT2 receptor mRNA expression in the WT retina was determined by in situ hybridization and the daily regulation in the ERG was investigated using LKC Technologies system as previously described (see: Baba et al., PNAS 106: 15043-8; 2009).
MT2transcripts were detected in the outer nuclear layer (ONL), inner nuclear layer (INL), but not in ganglion cell layer, by fluorescent in situ hybridization. MT2mRNA was abundant in the ONL, the retinal layer containing the nuclei of the photoreceptor cells, and the INL, where the cell bodies of horizontal, bipolar, amacrine, and Muller cells are located. A diurnal rhythm in the dark-adapted ERG responses was observed in WT mice, with higher a- and b-wave amplitudes at night, but this rhythm was absent in mice lacking MT2 receptors. Injection of melatonin (i.p., 1 mg/kg) during the day decreased the scotopic response threshold and the amplitude of the a- and b-waves in the WT mice, but not in the MT2-/- mice.
Our data indicate that the distribution of the MT2 receptor mRNA in the mouse retina is similar to distribution of the MT1 receptor and that removal of MT2 receptor induces similar effects of those reported for the mice lacking the MT1 receptor. Our results demonstrate that both melatonin receptor types are required for the diurnal rhythm in the dark-adapted ERG responses and suggest that MT1 and MT2 receptors may form heteromers in the photoreceptor cells, as reported by in vitro studies on HEK 293 cells.
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