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The absence of melanopsin alters retinal clock function and dopamine regulation by light

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An Erratum to this article was published on 12 July 2013

Abstract

The retinal circadian clock is crucial for optimal regulation of retinal physiology and function, yet its cellular location in mammals is still controversial. We used laser microdissection to investigate the circadian profiles and phase relations of clock gene expression and Period gene induction by light in the isolated outer (rods/cones) and inner (inner nuclear and ganglion cell layers) regions in wild-type and melanopsin-knockout (Opn −/− 4 ) mouse retinas. In the wild-type mouse, all clock genes are rhythmically expressed in the photoreceptor layer but not in the inner retina. For clock genes that are rhythmic in both retinal compartments, the circadian profiles are out of phase. These results are consistent with the view that photoreceptors are a potential site of circadian rhythm generation. In mice lacking melanopsin, we found an unexpected loss of clock gene rhythms and of the photic induction of Per1-Per2 mRNAs only in the outer retina. Since melanopsin ganglion cells are known to provide a feed-back signalling pathway for photic information to dopaminergic cells, we further examined dopamine (DA) synthesis in Opn −/− 4 mice. The lack of melanopsin prevented the light-dependent increase of tyrosine hydroxylase (TH) mRNA and of DA and, in constant darkness, led to comparatively high levels of both components. These results suggest that melanopsin is required for molecular clock function and DA regulation in the retina, and that Period gene induction by light is mediated by a melanopsin-dependent, DA-driven signal acting on retinal photoreceptors.

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Acknowledgments

We thank C. Gronfier and G. Gingras for critical reading of the manuscript, S. Hattar for the gift of the Opn −/− 4 mice. This research was supported by Rhône-Alpes CMIRA, ANR-09-MNPS-040, Retina France, Volubilis, GDRI Neurosciences, Cluster Handicap Vieillissement Neurosciences. The authors declare no competing financial interests.

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Authors and Affiliations

  1. Department of Chronobiology, INSERM U846, Stem Cell and Brain Research Institute, 18 Avenue du Doyen Lépine, 69500, Bron, France

    Ouria Dkhissi-Benyahya, Christine Coutanson, Kenneth Knoblauch, Hasna Lahouaoui, Vincent Leviel & Howard M. Cooper

  2. Université de Lyon, Lyon 1, UMR-S 846, 69003, Lyon, France

    Ouria Dkhissi-Benyahya, Christine Coutanson, Kenneth Knoblauch, Hasna Lahouaoui, Vincent Leviel & Howard M. Cooper

  3. Laboratoire de Pharmacologie, Neurobiologie et Comportement, Université Cadi Ayyad, Marrakech, Morocco

    Hasna Lahouaoui & Mohamed Bennis

  4. Faculté de Médecine et de Pharmacie de Lyon, ProfileXpert-LCMT, 69373, Lyon, France

    Catherine Rey

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  1. Ouria Dkhissi-Benyahya
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Correspondence to Ouria Dkhissi-Benyahya.

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Dkhissi-Benyahya, O., Coutanson, C., Knoblauch, K. et al. The absence of melanopsin alters retinal clock function and dopamine regulation by light. Cell. Mol. Life Sci. 70, 3435–3447 (2013). https://doi.org/10.1007/s00018-013-1338-9

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