Neuropsin (OPN5)-mediated photoentrainment of local circadian oscillators in mammalian retina and cornea

Ethan D. Buhr, Wendy W.S. Yue, Xiaozhi Ren, Zheng Jiang, Hsi Wen Rock Liao, Xue Mei, Shruti Vemaraju, Minh Thanh Nguyen, Randall R. Reed, Richard A. Lang, King Wai Yau, Russell N. Van Gelder

Research output: Contribution to journalArticlepeer-review


The molecular circadian clocks in the mammalian retina are locally synchronized by environmental light cycles independent of the suprachiasmatic nuclei (SCN) in the brain. Unexpectedly, this entrainment does not require rods, cones, or melanopsin (OPN4), possibly suggesting the involvement of another retinal photopigment. Here, we show that the ex vivo mouse retinal rhythm is most sensitive to short-wavelength light but that this photoentrainment requires neither the short-wavelength-sensitive cone pigment [S-pigment or cone opsin (OPN1SW)] nor encephalopsin (OPN3). However, retinas lacking neuropsin (OPN5) fail to photoentrain, even though other visual functions appear largely normal. Initial evidence suggests that OPN5 is expressed in select retinal ganglion cells. Remarkably, the mouse corneal circadian rhythm is also photoentrainable ex vivo, and this photoentrainment likewise requires OPN5. Our findings reveal a light-sensing function for mammalian OPN5, until now an orphan opsin.

Original languageEnglish (US)
Pages (from-to)13093-13098
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number42
StatePublished - Oct 20 2015


  • Circadian rhythm
  • Cornea
  • OPN5
  • Photoentrainment
  • Retina

ASJC Scopus subject areas

  • General


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