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

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.