Melanopsin- and L-cone-induced pupil constriction is inhibited by S- and M-cones in humans

Significance Human retinas contain five light-responsive cell types: rods; short (S)-, mid (M)-, and long (L)-wavelength–sensitive cones; and melanopsin-expressing ganglion cells. Intrinsically light-sensitive retinal ganglion cells (RGCs) also relay rod and cone information to brain areas involved in nonvisual responses, such as pupil constriction. Cones allow for visual color discrimination. How cone-dependent color discrimination affects nonvisual responses is poorly understood. We show that selectively activating L-cones or melanopsin constricts the pupil whereas S- or M-cone activation paradoxically dilates the pupil. Intrinsically photosensitive RGCs therefore appear to signal color on yellow/blue and red/green scales, with blue and green cone shifts being processed as brightness decrements. These findings are crucial in understanding brightness coding for visual and nonvisual responses such as circadian entrainment and alerting effects of light.
The human retina contains five photoreceptor types: rods; short (S)-, mid (M)-, and long (L)-wavelength–sensitive cones; and melanopsin-expressing ganglion cells. Recently, it has been shown that selective increments in M-cone activation are paradoxically perceived as brightness decrements, as opposed to L-cone increments. Here we show that similar effects are also observed in the pupillary light response, whereby M-cone or S-cone increments lead to pupil dilation whereas L-cone or melanopic illuminance increments resulted in pupil constriction. Additionally, intermittent photoreceptor activation increased pupil constriction over a 30-min interval. Modulation of L-cone or melanopic illuminance within the 0.25–4-Hz frequency range resulted in more sustained pupillary constriction than light of constant intensity. Opposite results were found for S-cone and M-cone modulations (2 Hz), mirroring the dichotomy observed in the transient responses. The transient and sustained pupillary light responses therefore suggest that S- and M-cones provide inhibitory input to the pupillary control system when selectively activated, whereas L-cones and melanopsin response fulfill an excitatory role. These findings provide insight into functional networks in the human retina and the effect of color-coding in nonvisual responses to light, and imply that nonvisual and visual brightness discrimination may share a common pathway that starts in the retina.