Localization of Melatonin Receptor 1 in Mouse Retina and Its Role in the Circadian Regulation of the Electroretinogram and Dopamine Levels

Anamika Sengupta,Kenkichi Baba,Francesca Mazzoni,Gianluca Tosini,Enrica Strettoi,Nikita V Pozdeyev,P Michael Iuvone,Shin Yamazaki

doi:10.1371/journal.pone.0024483

Anamika Sengupta, Kenkichi Baba + Show 6 more

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https://doi.org/10.1371/journal.pone.0024483

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Abstract

Melatonin modulates many important functions within the eye by interacting with a family of G-protein-coupled receptors that are negatively coupled with adenylate cyclase. In the mouse, Melatonin Receptors type 1 (MT1) mRNAs have been localized to photoreceptors, inner retinal neurons, and ganglion cells, thus suggesting that MT1 receptors may play an important role in retinal physiology. Indeed, we have recently reported that absence of the MT1 receptors has a dramatic effect on the regulation of the daily rhythm in visual processing, and on retinal cell viability during aging. We have also shown that removal of MT1 receptors leads to a small (3–4 mmHg) increase in the level of the intraocular pressure during the night and to a significant loss (25–30%) in the number of cells within the retinal ganglion cell layer during aging. In the present study we investigated the cellular distribution in the C3H/f+/+ mouse retina of MT1 receptors using a newly developed MT1 receptor antibody, and then we determined the role that MT1 signaling plays in the circadian regulation of the mouse electroretinogram, and in the retinal dopaminergic system. Our data indicate that MT1 receptor immunoreactivity is present in many retinal cell types, and in particular, on rod and cone photoreceptors and on intrinsically photosensitive ganglion cells (ipRGCs). MT1 signaling is necessary for the circadian rhythm in the photopic ERG, but not for the circadian rhythm in the retinal dopaminergic system. Finally our data suggest that the circadian regulation of dopamine turnover does not drive the photopic ERG rhythm.

Highlights

Previous studies have shown that melatonin is synthesized in the eyes of most vertebrates, where it is believed to modulate many important functions [1]
Western blotting of the melatonin receptor type 1 (MT1) receptor in the mouse retina showed an immunoreactive band of about 40 kDa in the retina of the with C3H/f+/+ (WT), but not in the MT12/2 mice (Figure 1, Top)
The focus of this study was to investigate the distribution of MT1 receptors in the retina using a newly developed antibody, and to determine the effects of MT1 signaling removal on the circadian regulation of the mouse ERGs and on the retinal dopaminergic system

Summary

Introduction

Previous studies have shown that melatonin is synthesized in the eyes of most vertebrates, where it is believed to modulate many important functions [1]. Immunoreactivity to melatonin receptor type 1 (MT1) has been located at the photoreceptors, in the inner retinal neurons and on ganglion cells (GCs) [3]. MT1 mRNAs have been localized to photoreceptors, inner retinal neurons, and GCs [4]. Since the vast majority of mouse strains are genetically incapable of synthesizing melatonin in the pineal and retina [5,6], the effects of melatonin receptor removal on retinal physiology in melatonin-proficient and melatonin-deficient mice are not well understood. We have shown that absence of MT1 receptors leads to a small (3–4 mmHg) increase in the level of intraocular pressure during the night, and to a significant loss (25–30%) in the number of cells within the retinal GC layer during aging [7]

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