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

Sep 23, 2015Proceedings of the National Academy of Sciences of the United States of America

Light resets daily rhythms in the eye’s retina and cornea through the protein Neuropsin (OPN5)

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Abstract

Mouse retinal rhythms are most sensitive to short-wavelength light but do not require traditional photoreceptors.

Molecular circadian clocks in the retina can synchronize with environmental light cycles independently of brain input.
Unexpectedly, existing photoreceptors like rods, cones, and melanopsin are not necessary for this synchronization.
Retinas lacking neuropsin (OPN5) fail to respond to light for circadian rhythm synchronization, despite normal visual functions.
Initial evidence indicates that OPN5 is found in specific retinal ganglion cells.
Corneal circadian rhythms also show light sensitivity ex vivo, which similarly depends on OPN5.

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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.

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

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