Ocular Photoreception for Circadian Rhythm Entrainment in Mammals.

Abstract

Circadian rhythms are self-sustained, approximately 24-h rhythms of physiology and behavior. These rhythms are entrained to an exactly 24-h period by the daily light-dark cycle. Remarkably, mice lacking all rod and cone photoreceptors still demonstrate photic entrainment, an effect mediated by intrinsically photosensitive retinal ganglion cells (ipRGCs). These cells utilize melanopsin (OPN4) as their photopigment. Distinct from the ciliary rod and cone opsins, melanopsin appears to function as a stable photopigment utilizing sequential photon absorption for its photocycle; this photocycle, in turn, confers properties on ipRGCs such as sustained signaling and resistance from photic bleaching critical for an irradiance detection system. The retina itself also functions as a circadian pacemaker that can be autonomously entrained to light-dark cycles. Recent experiments have demonstrated that another novel opsin, neuropsin (OPN5), is required for this entrainment, which appears to be mediated by a separate population of ipRGCs. Surprisingly, the circadian clock of the mammalian cornea is also light entrainable and is also neuropsin-dependent for this effect. The retina thus utilizes a surprisingly broad array of opsins for mediation of different light-detection tasks.