The photopigment in the human eye that transduces light for circadian and neuroendocrine regulation, is unknown. The aim of this study was to establish an action spectrum for light-induced melatonin suppression that could help elucidate the ocular photoreceptor system for regulating the human pineal gland. Subjects (37 females, 35 males, mean age of 24.5 ± 0.3 years) were healthy and had normal color vision. Full-field, monochromatic light exposures took place between 2:00 and 3:30 A.M. while subjects9 pupils were dilated. Blood samples collected before and after light exposures were quantified for melatonin. Each subject was tested with at least seven different irradiances of one wavelength with a minimum of 1 week between each nighttime exposure. Nighttime melatonin suppression tests (n = 627) were completed with wavelengths from 420 to 600 nm. The data were fit to eight univariant, sigmoidal fluence–response curves (R² = 0.81–0.95). The action spectrum constructed from these data fit an opsin template (R² = 0.91), which identifies 446–477 nm as the most potent wavelength region providing circadian input for regulating melatonin secretion. The results suggest that, in humans, a single photopigment may be primarily responsible for melatonin suppression, and its peak absorbance appears to be distinct from that of rod and cone cell photopigments for vision. The data also suggest that this new photopigment is retinaldehyde based. These findings suggest that there is a novel opsin photopigment in the human eye that mediates circadian photoreception.

The circadian and neurobehavioral effects of light are primarily mediated by a retinal ganglion cell photoreceptor in the mammalian eye containing the photopigment melanopsin. Nine action spectrum studies using rodents, monkeys, and humans for these responses indicate peak sensitivities in the blue region of the visible spectrum ranging from 459 to 484 nm, with some disagreement in short-wavelength sensitivity of the spectrum. The aim of this work was to quantify the sensitivity of human volunteers to monochromatic 420-nm light for plasma melatonin suppression. Adult female ( n = 14) and male ( n = 12) subjects participated in 2 studies, each employing a within-subjects design. In a fluence-response study, subjects ( n = 8) were tested with 8 light irradiances at 420 nm ranging over a 4-log unit photon density range of 10¹⁰ to 10¹⁴ photons/cm ²/sec and 1 dark exposure control night. In the other study, subjects ( n = 18) completed an experiment comparing melatonin suppression with equal photon doses (1.21 × 10¹³ photons/cm²/sec) of 420 nm and 460 nm monochromatic light and a dark exposure control night. The first study demonstrated a clear fluence-response relationship between 420-nm light and melatonin suppression ( p < 0.001) with a half-saturation constant of 2.74 × 10¹¹ photons/cm²/sec. The second study showed that 460-nm light is significantly stronger than 420-nm light for suppressing melatonin ( p < 0.04). Together, the results clarify the visible short-wavelength sensitivity of the human melatonin suppression action spectrum. This basic physiological finding may be useful for optimizing lighting for therapeutic and other applications.

Architectural lighting has potent biological effects but applied lighting practices that capitalize on this potential have been limited. In this review, we endeavor to consolidate and synthesize key references that will be useful for lighting professionals, with the goal of supporting knowledge translation into pragmatic lighting strategies. Specifically, we explain relevant terminology, outline basic concepts, identify key references, provide a balanced overview of the current state of knowledge, and highlight important remaining questions. We summarize the physiological effects of light on human health and well-being, including a description of the processes underlying the photic regulation of circadian, neuroendocrine, and neurobehavioral functions. We review seminal work elucidating the elements mediating the potency of light for these physiological responses, with specific attention to factors critical for interpreting those findings. In parallel, we explain and endorse melanopic Equivalent Daylight Illuminance ( $E_{\mathrm{v},\mathrm{m}\mathrm{e}\mathrm{l}}^{\mathrm{D}65}$) as the preferred measure to quantify the biological potency of light. Ultimately, while future studies are necessary to further facilitate the translation of laboratory knowledge to domestic and workplace settings, the immediate potential for applied lighting to better support human health is clear. Aiming for integrative lighting solutions that have biologically high potency light during the day and low potency during the night is perhaps the most immediate improvement to be made in order to better support applications for humans.

Illumination of different areas of the human retina elicits differences in acute light-induced suppression of melatonin. The aim of this study was to compare changes in plasma melatonin levels when light exposures of equal illuminance and equal photon dose were administered to superior, inferior, and full retinal fields. Nine healthy subjects participated in the study. Plexiglass eye shields were modified to permit selective exposure of the superior and inferior halves of the retinas of each subject. The Humphrey Visual Field Analyzer was used both to confirm intact full visual fields and to quantify exposure of upper and lower visual fields. On study nights, eyes were dilated, and subjects were exposed to patternless white light for 90 min between 0200 and 0330 under five conditions: (1) full retinal exposure at 200 lux, (2) full retinal exposure at 100 lux, (3) inferior retinal exposure at 200 lux, (4) superior retinal exposure at 200 lux, and (5) a dark-exposed control. Plasma melatonin levels were determined by radioimmunoassay. ANOVA demonstrated a significant effect of exposure condition (F = 5.91, p < 0.005). Post hoc Fisher PLSD tests showed significant (p [#003C] 0.05) melatonin suppression of both full retinal exposures as well as the inferior retinal exposure; however, superior retinal exposure was significantly less effective in suppressing melatonin. Furthermore, suppression with superior retinal exposure was not significantly different from that of the dark control condition. The results indicate that the inferior retina contributes more to the light-induced suppression of melatonin than the superior retina at the photon dosages tested in this study. Findings suggest a greater sensitivity or denser distribution of photoreceptors in the inferior retina are involved in light detection for the retinohypothalamic tract of humans.