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The mammalian retina captures a multitude of diverse features from the external environment and conveys them via the optic nerve to a myriad of retinorecipient nuclei. Understanding how retinal signals act in distinct brain functions is one of the most central and established goals of neuroscience. Using the common marmoset ( Callithrix jacchus ), a monkey from Northeastern Brazil, as an animal model for parsing how retinal innervation works in the brain, started decades ago due to their marmoset’s small bodies, rapid reproduction rate, and brain features. In the course of that research, a large amount of new and sophisticated neuroanatomical techniques was developed and employed to explain retinal connectivity. As a consequence, image and non-image-forming regions, functions, and pathways, as well as retinal cell types were described. Image-forming circuits give rise directly to vision, while the non-image-forming territories support circadian physiological processes, although part of their functional significance is uncertain. Here, we reviewed the current state of knowledge concerning retinal circuitry in marmosets from neuroanatomical investigations. We have also highlighted the aspects of marmoset retinal circuitry that remain obscure, in addition, to identify what further research is needed to better understand the connections and functions of retinorecipient structures.

Glaucoma is a blindness-causing disease that involves selective damage to retinal ganglion cells (RGCs) and their axons. A subset of RGCs expressing the photopigment melanopsin regulates non-image-forming visual system functions, such as pupillary light reflex and circadian rhythms. We analyzed the effect of melatonin on the non-image-forming visual system alterations induced by experimental glaucoma. For this purpose, male Wistar rats were weekly injected with vehicle or chondroitin sulfate into the eye anterior chamber. The non-image-forming visual system was analyzed in terms of (1) melanopsin-expressing RGC number, (2) anterograde transport from the retina to the olivary pretectal nucleus and the suprachiasmatic nuclei, (3) blue- and white light-induced pupillary light reflex, (4) light-induced c-Fos expression in the suprachiasmatic nuclei, (5) daily rhythm of locomotor activity, and (6) mitochondria in melanopsin-expressing RGC cells. Melatonin prevented the effect of experimental glaucoma on melanopsin-expressing RGC number, blue- and white light-induced pupil constriction, retina-olivary pretectal nucleus, and retina- suprachiasmatic nuclei communication, light-induced c-Fos expression in the suprachiasmatic nuclei, and alterations in the locomotor activity daily rhythm. In addition, melatonin prevented the effect of glaucoma on melanopsin-expressing RGC mitochondrial alterations. These results support that melatonin protected the non-image-forming visual system against glaucoma, probably through a mitochondrial protective mechanism.

Light is the paramount environmental signal for the entrainment of endogenous circadian rhythms. Its non-visual effects, mediated by the retina, exert a profound control over human sleep, mood and systemic physiological homeostasis. Beyond its canonical function in image formation, the retina operates as a primary irradiance detector through a specialized class of neurons, the intrinsically photosensitive retinal ganglion cells (ipRGCs), which utilize the photopigment melanopsin. These cells convey environmental light information directly to the suprachiasmatic nucleus (SCN), the brain's master circadian pacemaker, thereby synchronizing the body's internal timekeeping with the external solar cycle. Compelling evidence demonstrates that the spectral quality of light, particularly within the short-wavelength blue range, potently modulates neuroendocrine and neural systems via the ipRGC pathway, governing melatonin synthesis, the architecture of the sleep-wake cycle and affective regulation. The modern light environment, characterized by ubiquitous artificial light at night and pathological states of light perception resulting from ophthalmic diseases such as glaucoma and retinal degenerations, can severely disrupt this synchronization. The consequent circadian misalignment is a significant etiological factor in sleep disorders, depressive symptoms and other systemic morbidities. The retina's integral position within the light-rhythm-behavior axis is thus a critical nexus between the visual system and systemic physiology. In addition, the present study outlined the nitric oxide-cyclic GMP signaling axis in SCN as a critical mediator of photic entrainment. This review provided an in-depth analysis from an ophthalmic perspective, synthesizing evidence from animal models and human studies to dissect the complex molecular, cellular and network-level mechanisms of retinal circadian regulation, explore how aberrant photic signaling impacts sleep and mood and critically evaluate the potential of targeted interventions such as light therapy and spectral management in the context of rhythm-related disorders.

Physiological effects of light exposure in humans are diverse. Among them, the circadian rhythm phase shift effect in order to maintain a 24-h cycle of the biological clock is referred to as non-visual effects of light collectively with melatonin suppression and pupillary light reflex. The non-visual effects of light may differ depending on age, and clarifying age-related differences in the non-visual effects of light is important for providing appropriate light environments for people of different ages. Therefore, in various research fields, including physiological anthropology, many studies on the effects of age on non-visual functions have been carried out in older people, children and adolescents by comparing the effects with young adults. However, whether the non-visual effects of light vary depending on age and, if so, what factors contribute to the differences have remained unclear. In this review, results of past and recent studies on age-related differences in the non-visual effects of light are presented and discussed in order to provide clues for answering the question of whether non-visual effects of light actually vary depending on age. Some studies, especially studies focusing on older people, have shown age-related differences in non-visual functions including differences in melatonin suppression, circadian phase shift and pupillary light reflex, while other studies have shown no differences. Studies showing age-related differences in the non-visual effects of light have suspected senile constriction and crystalline lens opacity as factors contributing to the differences, while studies showing no age-related differences have suspected the presence of a compensatory mechanism. Some studies in children and adolescents have shown that children’s non-visual functions may be highly sensitive to light, but the studies comparing with other age groups seem to have been limited. In order to study age-related differences in non-visual effects in detail, comparative studies should be conducted using subjects having a wide range of ages and with as much control as possible for intensity, wavelength component, duration, circadian timing, illumination method of light exposure, and other factors (mydriasis or non-mydriasis, cataracts or not in the older adults, etc.).

Modern indoor lighting faces the challenge of finding an appropriate balance between energy consumption, legal requirements, visual performance, and the circadian effectiveness of a spectrum. Multi-channel LED luminaires have the option of keeping image-forming metrics steady while varying the melanopic radiance through metamer spectra for non-visual purposes. Here, we propose the theoretical concept of an automated smart lighting system that is designed to satisfy the user’s visual preference through neural networks while triggering the non-visual pathway via metamers. To quantify the melanopic limits of metamers at a steady chromaticity point, we have used 561 chromaticity coordinates along the Planckian locus (2700 K to 7443 K, ±Duv 0 to 0.048) as optimisation targets and generated the spectra by using a 6-channel, 8-channel, and 11-channel LED combination at three different luminance levels. We have found that in a best-case scenario, the melanopic radiance can be varied up to 65% while keeping the chromaticity coordinates constant (Δu′v′≤7.05×10−5) by using metamer spectra. The highest melanopic metamer contrast can be reached near the Planckian locus between 3292 and 4717 K within a Duv range of −0.009 to 0.006. Additionally, we publish over 1.2 million optimised spectra generated by multichannel LED luminaires as an open-source dataset along with this work.

Background Although evidence of both beneficial and adverse biological effects of lighting has accumulated, biologically favorable lighting often does not match subjectively comfortable lighting. By controlling the correlated color temperature (CCT) of ambient lights, we investigated the feasibility of combined lighting that meets both biological requirements and subjective comfort. Methods Two types of combined lightings were compared; one consisted of a high-CCT (12000 K) light-emitting diode (LED) panel as the ambient light and a low-CCT (5000 K) LED stand light as the task light (high-low combined lighting), and the other consisted of a low-CCT (4500 K) LED panel as the ambient light and the same low-CCT (5000 K) stand light as the task light (low-low combined lighting) as control. Ten healthy subjects (5 young and 5 elderly) were exposed to the two types of lighting on separate days. Autonomic function by heart rate variability, psychomotor performances, and subjective comfort were compared. Results Both at sitting rest and during psychomotor workload, heart rate was higher and the parasympathetic index of heart rate variability was lower under the high-low combined lighting than the low-low combined lighting in both young and elderly subject groups. Increased psychomotor alertness in the elderly and improved sustainability of concentration work performance in both age groups were also observed under the high-low combined lighting. However, no significant difference was observed in the visual-analog-scale assessment of subjective comfort between the two types of lightings. Conclusions High-CCT ambient lighting, even when used in combination with low-CCT task lighting, could increase autonomic and psychomotor arousal levels without compromising subjective comfort. This finding suggests the feasibility of independent control of ambient and task lighting as a way to achieve both biological function regulation and subjective comfort.

Background Exposures to melanopsin-stimulating (melanopic) component-rich blue light enhance arousal level. We examined their effects in office workers. Main body of abstract Eight healthy university office workers were exposed to blue and orange lights for 30 min during lunch break on different days. We compared the effects of light color on autonomic arousal level assessed by heart rate variability (HRV) and behavioral alertness by psychomotor vigilance tests (PVT). Heart rate was higher and high-frequency (HF, 0.150.45 Hz) power of HRV was lower during exposure to the blue light than to orange light. No significant difference with light color was observed, however, in any HRV indices during PVT or in PVT performance after light exposure. Short conclusion Exposure to blue light during lunch break, compared with that to orange light, enhances autonomic arousal during exposure, but has no sustained effect on autonomic arousal or behavioral alertness after exposure.

Objective Blue light has been attributed to the adverse biological effects caused by the use of smartphones and tablet devices at night. However, it is not realistic to immediately avoid nighttime exposure to blue light in the lifestyle of modern society, so other effective methods should be investigated. Earlier studies reported that inferior retinal light exposure causes greater melatonin suppression than superior retinal exposure. We examined whether the autonomic responses to blue light depends on the angle of incidence to the eye. Results In eight healthy subjects, blue light from organic electroluminescent lighting device (15.4 lx at subjects’ eye) was exposed from 6 angles (0º, 30º, 45º, 135º, 150º, and 180º) for 5 min each with a 10-min interval of darkness. After adjusting the order effect of angles, however, no significant difference in heart rate or autonomic indices of heart rate variability with the angle of incidence was detected in this study.

Background Blue light containing rich melanopsin-stimulating (melanopic) component has been reported to enhance arousal level, but it is unclear whether the determinant of the effects is the absolute or relative content of melanopic component. We compared the autonomic and psychomotor arousal effects of melanopic-enriched blue light of organic light-emitting diode (OLED) with those of OLED lights with lesser absolute amount of melanopic component (green light) and with greater absolute but lesser relative content (white light). Methods Using a ceiling light consisting of 120 panels (55 × 55 mm square) of OLED modules with adjustable color and brightness, we examined the effects of blue, green, and white lights (melanopic photon flux densities, 0.23, 0.14, and 0.38 μmol/m 2 /s and its relative content ratios, 72, 17, and 14%, respectively) on heart rate variability (HRV) during exposures and on the performance of psychomotor vigilance test (PVT) after exposures in ten healthy subjects with normal color vision. For each of the three colors, five consecutive 10-min sessions of light exposures were performed in the supine position, interleaved by four 10-min intervals during which 5-min PVT was performed under usual fluorescent light in sitting position. Low-frequency (LF, 0.04–0.15 Hz) and high-frequency (HF, 0.15–0.40 Hz) power and LF-to-HF ratio (LF/HF) of HRV during light exposures and reaction time (RT) and minor lapse (RT >500 ms) of PVT were analyzed. Results Heart rate was higher and the HF power reflecting autonomic resting was lower during exposures to the blue light than the green and white lights, while LF/HF did not differ significantly. Also, the number of minor lapse and the variation of reaction time reflecting decreased vigilance were lower after exposures to the blue light than the green light. Conclusions The effects of blue OLED light for maintaining autonomic and psychomotor arousal levels depend on both absolute and relative contents of melanopic component in the light.