Regulation of tryptophan hydroxylase expression by a retinal circadian oscillator in vitro

Carla B. Green, Gregory M. Cahill, Joseph C. Besharse

Research output: Contribution to journalArticlepeer-review

47 Scopus citations


Many aspects of retinal physiology are controlled by a circadian clock including at least two steps in the melatonin synthetic pathway: the activity of the enzyme,N-acetyltransferase (NAT), and mRNA levels of the rate-limiting enzyme tryptophan hydroxylase (TPH). Light and dopamine (through D2-like dopamine receptors) can phase shift the clock, and can also acutely inhibit NAT activity, resulting in supressed melatonin synthesis. In this paper, we show that eyecups cultured in constant darkness maintain a clock-controlled rhythm in TPH mRNA, with low levels in early day, rising to a peak in early night. Both eyecups and isolated retinas, cultured in light during the day, also exhibit a similar increase in TPH mRNA levels, indicating that this expression is not acutely inhibited by light. Treatment with light or quinpirole (D2 dopamine receptor agonist) in early night, at a time and dose that acutely inhibits NAT activity, does not change levels of TPH mRNA. Addition of eticlopride (D2 dopamine receptor antagonist) during the day, also has no effect on the normal daytime increase in TPH message levels. Therefore, TPH mRNA level is controlled by a circadian clock located within the eye, but acute effects of light or dopamine are not detected.

Original languageEnglish (US)
Pages (from-to)283-290
Number of pages8
JournalBrain Research
Issue number2
StatePublished - Apr 24 1995


  • Circadian
  • Dopamine
  • Light
  • Melatonin
  • Retina
  • Serotonin
  • Tryptophan hydroxylase
  • Xenopus

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology


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