Roles of the nonvisual opsins in the mammalian retina

In addition to the rods and cones that subserve vision, several classes of mammalian retinal ganglion cells are also directly photoreceptive. These "intrinsically photosensitive" retinal ganglion cells ("ipRGCs") utilize the nonvisual photopigments melanopsin (Opn4), neuropsin (Opn5), and encephalopsin (Opn3), which are expressed in largely nonoverlapping ganglion cell populations. Remarkably, all three nonvisual opsins appear to influence the circadian clock, but in different ways. Opn4-expressing cells project from the retina to brain regions regulating circadian rhythms, such as the suprachiasmatic nuclei, and are necessary for entrainment of the behavioral clock in mammals to external light-dark cycles. The retina itself is also a functioning circadian clock, and its local entrainment is mediated by Opn5-dependent photoreception. While evidence for Opn3 functioning as a nonvisual photoreceptor is more limited, loss of its function impairs the amplitude of the circadian clock in multiple tissues, including the retina. These opsins also have other functions within and outside the eye, with Opn4-expressing cells in particular having been shown to influence form vision. This review summarizes current understanding of the biochemistry, cell biology, and physiology of the three nonvisual opsins in the retina.