Melanopsin cells are the principal conduits for rod–cone input to non-image-forming vision

Abstract

Rod and cone photoreceptors detect light and relay this information through a multisynaptic pathway to the brain via retinal ganglion cells (RGCs) 1 . These retinal outputs support not only pattern vision, but also non-image forming (NIF) functions, which include circadian photoentrainment and pupillary light reflex (PLR). In mammals, NIF functions are mediated by rods, cones and the melanopsincontaining intrinsically photosensitive retinal ganglion cells (ipRGCs) 2, 3 . Rod/cone photoreceptors and ipRGCs are complementary in signalling light intensity for NIF functions 4-12 . The ipRGCs, in addition to being directly photosensitive, also receive synaptic input from rod/cone networks 13, 14 . To determine how the ipRGCs relay rod/cone light information for both image and non-image forming functions, we genetically ablated ipRGCs in mice. Here we show that animals lacking ipRGCs retain pattern vision, but have deficits in both PLR and circadian photoentrainment that are more extensive than those observed in melanopsin knockouts 8,10,11 . The defects in PLR and photoentrainment resemble those observed in animals that lack phototransduction in all three †To whom correspondence should be addressed.

Functional evaluation of iodoacetic acid induced photoreceptor degeneration in the cat

“…Nevertheless, the present result reveals that complete removal of conventional photoreceptors substantially reduced but did not completely abolish PLR. Thus our result is in agreement with previous reports [25][26][27] and suggests that the residual PLR could be contributed by surviving ipRGCs.…”

“…It is expected because light signal is sensed by two different types of photoreceptors, the conventional photoreceptors and intrinsically photosensitive retinal ganglion cells or melanopsin expressing retinal ganglion cells (ipRGCs), and the latter is much less sensitive than conventional photoreceptors [25]. Although there is substantial evidence that both conventional photoreceptors and ipRGCs contribute to PLR, depleting ipRGCs could substantially diminish PLR [25][26][27]. Since there is no melanopsin antibody available that specifically targets ipRGCs in the cat, we cannot evaluate the impact of IAA on ipRGCs in the cats.…”

Signalling by melanopsin (OPN4) expressing photosensitive retinal ganglion cells

“…However, the timeline with which M1 cells innervate the shell of the OPN coincides with the development of the PLR, 37 and the selective ablation of M1-type pRGCs has been shown to severely impair the PLR. 47 Therefore it would seem that the PLR is driven by M1-type pRGCs, and thus distinct subsets of M1-type pRGCs are responsible for driving circadian entrainment and the PLR. Unfortunately, the roles performed by other classes of pRGC are less clear.…”

Glucocorticoids and circadian clock control of cell proliferation: At the interface between three dynamic systems

“…Their function is crucial for entrainment of the SCN, since transgenic animals in which these cells are genetically ablated show free-running rhythms when exposed to light-dark cycles, just as normal animals do under constant darkness [10]. The photopigments of the rods and cones of the retina and melanopsin are highly redundant in this process, because only animals that lack both functional rods and cones and melanopsin show this "circadian blindness", whereas the presence of one of the two systems is sufficient to maintain circadian entrainment [11].…”