May 2007
Volume 48, Issue 13
ARVO Annual Meeting Abstract  |   May 2007
Regulation of Circadian Clock in the Mammalian Retina
Author Affiliations & Notes
  • G.-X. Ruan
    Biological Sciences, Vanderbilt University, Nashville, Tennessee
  • S. Yamazaki
    Biological Sciences, Vanderbilt University, Nashville, Tennessee
  • D. G. McMahon
    Biological Sciences, Vanderbilt University, Nashville, Tennessee
  • Footnotes
    Commercial Relationships G. Ruan, None; S. Yamazaki, None; D.G. McMahon, None.
  • Footnotes
    Support NIH Grant EY015815
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 5973. doi:
  • Views
  • Share
  • Tools
    • Alerts
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      G.-X. Ruan, S. Yamazaki, D. G. McMahon; Regulation of Circadian Clock in the Mammalian Retina. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5973.

      Download citation file:

      © ARVO (1962-2015); The Authors (2016-present)

  • Supplements

Methods:: mPer2Luc C57BL/6J mice were backcrossed with C3H rd mice once to produce mPer2Luc knockin mice that were heterozygous for the rd gene and were genetically capable of producing melatonin. Retinas from these mice were isolated, cultured and assayed for circadian rhythms of the transgenic PER2::Luc reporter by luminescence. Drugs were applied to retinal explant cultures at the trough between the 2nd and 3rd peaks of PER2 expression rhythms in vitro, and then were left in the cultures.

Results:: Robust circadian rhythms of PER2::LUC expression sustained for up to 15 cycles in vitro without medium change with our modified retinal explant culture procedure. Circadian PER2 expression rhythms persisted during continuous activation or blockade of receptors for melatonin (10nM-10µM), dopamine (10µM-100µM), glycine (1mM-5mM), and glutamate (100µM-500µM). However, continuous application of γ-aminobutyric acid (GABA) inhibited PER2 expression in a dose-dependent manner. Prolonged application of 3 mM GABA reversibly disrupted the PER2 expression rhythms and stopped the retinal circadian clock based on restarted phase after washout. The inhibitory function of GABA was blunted by blockade of chloride channel-coupled GABAA and GABAC receptors.

Conclusions:: Our results indicate that intra-retinal communication via melatonin, dopamine, glycine, or glutamate is not necessary for rhythms generation by retinal circadian clocks and suggest that GABA may play an important role in regulating the circadian clock in the mammalian retina.

Keywords: circadian rhythms • retina • neurotransmitters/neurotransmitter systems 

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.