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Subspecialties Retina, Basic & Translational Research

Body Clock Control

Modern life comes with modern perils... International travel and night shifts both disrupt the circadian rhythm, which can lead to more serious health issues, such as depression and even cancer (1)(2) in the longer-term. Circadian rhythm control stems from the suprachiasmatic nucleus (SCN) in the hypothalamus, which releases various hormones and neuropeptides to set the pace. But fine-tuning comes from the retina – specifically from intrinsically photosensitive retinal ganglion cells (RGCs) that convey light information directly to the SCN where the neurotransmitter glutamate is released (3). But it turns out that this isn’t the whole story...

Now, a team of researchers has discovered another subpopulation of RGCs in rats that communicate directly with the SCN, signaling with the neuropeptide hormone vasopressin (4) – and are aptly named vasopressin-expressing RGCs (VP-RGCs). After showing that these cells project directly into the SCN, the team demonstrated that expression of Fos, a transcription factor implicated in the regulation of vasopressin synthesis, was significantly higher in VP-RGCs following light stimulation and that, in turn, light-evoked vasopressin release enhanced both the responses of SCN neurons to light, and the expression of c-fos in the SCN. The team reports, “Vasopressin, well known to be an important output of the SCN, is also a time-dependent mediator of light information from the retina to the SCN.”

But what about jet lag? With previous studies supporting a link between vasopressin and circadian rhythm misalignment (5), the new findings further support the potential of vasopressin as a therapeutic target. Lead author Mike Ludwig says, “Our exciting results show a potentially pharmacological route to manipulate our internal biological clock. Studies in the future which alter vasopressin signaling through the eye could lead to developing eye drops to get rid of jet lag, but we are still a long way off from this.”

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  1. AA Kondratova, RV Kondratov, “The circadian clock and pathology of the ageing brain”, Nat Rev Neurosci. 13, 325–335 (2012). PMID: 22395806.
  2. MH Hastings et al., “A clockwork web: circadian timing in brain and periphery, in health and disease”, Nat Rev Neurosci, 4, 649-661 (2003). PMID: 12894240.
  3. RJ Lucas, “Mammalian inner retinal photoreception”, Curr Biol, 23, R125-33 (2013). PMID: 23391390.
  4. T Tsuji et al., “Vasopressin casts light on the suprachiasmatic nucleus”, J Physiol, [Epub ahead of print] (2017). PMID: 28402052.
  5. Y Yamaguchi et al., “Mice genetically deficient in vasopressin V1a and V1b receptors are resistant to jet lag”, Science, 342, 85–90 (2013). PMID: 24092737.
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