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Contributed by King-Wai Yau, August 17, 2015 (sent for review July 22, 2015; reviewed by Carla B. Green and Christophe P. Ribelayga)
Significance
The behavioral circadian rhythms of mammals are synchronized to light/dark cycles through rods, cones, and melanopsin (OPN4)-expressing, intrinsically photosensitive ganglion cells in the retina. The molecular circadian rhythms in the mammalian retina are themselves synchronized to light/dark signals. We show here that this retinal photoentrainment, in an ex vivo setting, requires neuropsin (OPN5), an orphan opsin in mammals. Remarkably, the circadian clocks in the cornea are also photoentrained ex vivo in an OPN5-dependent manner.
Abstract
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.
Footnotes
↵1Present address: Department of Neurobiology, Harvard Medical School, Boston, MA 02115.
- ↵2To whom correspondence may be addressed. Email: kwyau{at}jhmi.edu or russvg{at}uw.edu.
Author contributions: E.D.B. and R.N.V.G. designed and performed all photoentrainment experiments; H.-W.R.L. made the Opn5−/− line 1; W.W.S.Y. characterized the Opn5−/− line 1; X.R. generated the Opn3−/− mouse line; W.W.S.Y. performed the X-Gal labelings (Opn5−/− line 1) and immunolabelings (line 1); S.V. performed the X-Gal labelings (line 2); W.W.S.Y. and Z.J. performed the CMFDG labeling and subsequent injection of Alexa dyes (line 1); R.R.R. provided invaluable advice on molecular biology and genetics; X.M., S.V., M.-T.N., and R.A.L generated and characterized the Opn5−/− line 2; and E.D.B., W.W.S.Y., R.A.L., K.-W.Y., and R.N.V.G wrote the paper.
Reviewers: C.B.G., University of Texas Southwestern Medical Center; and C.P.R., University of Texas Health Science Center at Houston.
The authors declare no conflict of interest.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1516259112/-/DCSupplemental.
Freely available online through the PNAS open access option.
OPN5-mediated photoentrainment in the eye
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