Melanopsin and Rod–Cone Photoreceptors Play Different Roles in Mediating Pupillary Light Responses during Exposure to Continuous Light in Humans

Abstract

In mammals, the pupillary light reflex is mediated by intrinsically photosensitive melanopsin-containing retinal ganglion cells that also receive input from rod-cone photoreceptors. To assess the relative contribution of melanopsin and rod-cone photoreceptors to the pupillary light reflex in humans, we compared pupillary light responses in normally-sighted individuals (n = 24) with a blind individual lacking rod-cone function. Here, we show that visual photoreceptors are required for normal pupillary responses to continuous light exposure at low irradiance levels, and for sustained pupillary constriction during exposure to light in the long-wavelength portion of the visual spectrum. In the absence of rod-cone function, pupillomotor responses are slow and sustained, and cannot track intermittent light stimuli, suggesting that rods/cones are required for encoding fast modulations in light intensity. In sighted individuals, pupillary constriction decreased monotonically for at least 30 minutes during exposure to continuous low-irradiance light, indicating that steady-state pupillary responses are an order of magnitude slower than previously reported. Exposure to low-irradiance intermittent green light (543 nm; 0.1–4 Hz) for 30 min, which was given to activate cone photoreceptors repeatedly, elicited sustained pupillary constriction responses that were more than twice as great compared to exposure to continuous green light. Our findings demonstrate non-redundant roles for rod-cone photoreceptors and melanopsin in mediating pupillary responses to continuous light. Moreover, our results suggest that it might be possible to enhance non-visual light responses to low-irradiance exposures by using intermittent light to activate cone photoreceptors repeatedly in humans.

Temporal integration of light flashes by the human circadian system

“…Underlying these NIF responses to light, traditional rod and cones photoreceptors are thought to be implicated in the fast and transient responses, whereas melanopsin is hypothesized to have a predominant effect on the sustainability and persistence of a response (33,34). To date, however, the integrative physiology light in a nonlinear fashion.…”

Why Directionality Is an Important Light Factor for Human Health to Consider in Lighting Design?

“…A fairly uniform distribution of the ipRGCs was reported by Moirn et al [25], Semo et al [37], and by Hughes et al [30] when all subtypes of ipRGCs have been taken into account. In addition, we should keep in mind that ipRGCs receive radiation stimuli not only intrinsically but also via the classical photoreceptors [3,30]. Hughes et al [30] have demonstrated the influence of both rods and cones on the spectral tuning of different subtypes of ipRGCs.…”

“…In this paper the authors therefore refer to radiation instead of light. The ipRGCs transduce radiation received directly and via the rods and cones [3,4] to neural signals which are transmitted to different parts of the brain, e.g., the Supra-Chiasmatic Nuclei (SCN). The SCN regulates a set of endogenous physiological and behavioral (e.g., circadian) rhythms through its connection to the central nervous system.…”

Unified framework to evaluate non-visual spectral effectiveness of light for human health

“…Studies on humans have demonstrated that both monochromatic short-wavelength light and blue-enriched polychromatic light are more effective than light at longer wavelengths at suppressing melatonin, [1][2][3] resetting the circadian clock, 4,5 enhancing alerting effects and cognitive function, 3,[6][7][8] and constricting the pupil. 9,10 These non-visual effects of light are primarily mediated by recently discovered intrinsically photosensitive retinal ganglion cells (ipRGCs). 11 These cells use melanopsin as a photopigment and, as a result, the ipRGCs are characterized by a spectral sensitivity curve that peaks in the short wavelength region around 490 nm, estimated in vivo, distinguished from the spectral sensitivity of rod and cone photoreceptors.…”