Rods contribute to the light-induced phase shift of the retinal clock in mammals.

Hugo Calligaro,Ouria Dkhissi-Benyahya,Nadia Mazzaro,Marie-Paule Felder-Schmittbuhl,Christine Coutanson,Howard M Cooper,Raymond P Najjar,Nasser Haddjeri,Paul Taghert

doi:10.1371/journal.pbio.2006211

Abstract

While rods, cones, and intrinsically photosensitive melanopsin-containing ganglion cells (ipRGCs) all drive light entrainment of the master circadian pacemaker of the suprachiasmatic nucleus, recent studies have proposed that entrainment of the mouse retinal clock is exclusively mediated by a UV-sensitive photopigment, neuropsin (OPN5). Here, we report that the retinal circadian clock can be phase shifted by short duration and relatively low-irradiance monochromatic light in the visible part of the spectrum, up to 520 nm. Phase shifts exhibit a classical photon dose-response curve. Comparing the response of mouse models that specifically lack middle-wavelength (MW) cones, melanopsin, and/or rods, we found that only the absence of rods prevented light-induced phase shifts of the retinal clock, whereas light-induced phase shifts of locomotor activity are normal. In a “rod-only” mouse model, phase shifting response of the retinal clock to light is conserved. At shorter UV wavelengths, our results also reveal additional recruitment of short-wavelength (SW) cones and/or OPN5. These findings suggest a primary role of rod photoreceptors in the light response of the retinal clock in mammals.

Highlights

The mammalian retina contains an endogenous timekeeping system that ensures the fine tuning of its physiology to daily changes in light intensity [1]
The mammalian retina contains a circadian clock that plays a crucial role in adapting retinal physiology and visual function to light/dark changes
Recent studies argue that none of these photoreceptors are involved in light responses of the retinal clock and propose that photoresponses are exclusively mediated by the UV-sensitive photopigment neuropsin (OPN5)

Summary

Introduction

The mammalian retina contains an endogenous timekeeping system that ensures the fine tuning of its physiology to daily changes in light intensity [1]. The retina plays a key role in photic entrainment of the central clock located in the suprachiasmatic nucleus (SCN) This response is mediated through intrinsically photosensitive melanopsin-containing retinal ganglion cells (ipRGCs) that receive inputs from rods and cones [18,19,20,21,22]. The landmark study by Ruan and colleagues demonstrated that the retinal clock is phase shifted by broadband white light [23]. In their model, ipRGCs and/or middle-wavelength (MW) cones were proposed to mediate lightinduced phase shifts through synaptic contacts conveying excitatory influences to dopaminergic amacrine cells [17,26,27,28,29,30,31]. Dopamine is well known to play a central role in the regulation of light-induced responses of the retinal clock [23,31,32,33,34,35]

Methods

Results

Discussion

Conclusion