Retinal Photopigments Research Articles

Diagnosis and management of transient smartphone blindness: A literature review

The development of smartphones worldwide has rapidly increased the number of smartphone users. Although smartphones have many benefits, prolonged use causes various visual disorders, of which transient smartphone blindness (TSB) is one of the most important concerns. This study aims to analyse the phenomenon of TSB and explore its etiology, pathophysiology, symptoms, and examination to determine the diagnosis and management. Transient smartphone blindness is a new physiologic phenomenon caused by exposure to a certain level of smartphone bright light and the body posture of the smartphone user. It leads to the use of monocular vision to stare at the smartphone. By exploring recent literature, this study found that patients with TSB experienced retinal photopigment bleaching, which decreased light sensitivity. Typically, the sensitivity returned physiologically after several minutes. Patients with this blindness showed several symptoms. For example, they perceived shapes, outlines, or figures during the blackout. The diagnosis of TSB should be primarily based on a detailed history of smartphone use, with the differential diagnosis based on circumstance or occurrence. This diagnosis is useful to distinguish it from transient ischemic attack (TIA). Transient smartphone blindness is a basic monocular transient loss that does not require therapy or drugs. However, it was found that the reassurance of patients’ condition and suggestions on smartphone use were sufficient for the intervention. With a limited scientific study of TSB, this review is the first to raise the discussion topic. It is expected to help physicians to diagnose TSB significantly. In addition, this study will enrich the literature, particularly on the scientific and clinical mechanisms of recognising TSB for clinical diagnosis and management.

Melanopsin enhances image persistence

Contributions of the inner retinal photopigment melanopsin to human visual perception are incompletely understood. Here, we use a four-primary display to produce stimuli differing in melanopsin versus cone contrast in psychophysical paradigms in eight subjects with normal color vision. We address two predictions from electrophysiological recordings of the melanopsin system in non-human mammals: melanopsin influences color and/or supports image persistence under visual fixation. We first construct chromatic contrast sensitivity contours for stimuli differing in melanopsin excitation presented as a central annulus (10°) or peripheral (22.5°) spot. We find that although including melanopsin contrast produces modest changes in the average chromatic coordinates in both eccentricities, this occurs equally at low (0.5Hz) and higher (3.75Hz) temporal frequencies, arguing that it reflects divergence in cone spectral sensitivity in our participants from that captured in standardized cone fundamentals rather than a melanopsin contribution to color. We continue to ask whether the established ability of melanopsin to sustain firing of visual neurons under extended light exposure has a visual correlate, using the optical illusion of Troxler fading in which blurred spots in periphery disappear during visual fixation. We find that introducing additional melanopsin contrast (+28% Michelson contrast) to either bright or dark spots increases fading latency by 35%± 8.8% and 41%± 13.6%, respectively. Our data argue that the primary contribution of melanopsin to perception under these conditions isnot to provide a color percept but rather to enhance persistence of low spatial frequency patterns during visual fixation.

Circadian and visual photometry.

Photometry is the metrology of light-optical radiation seen by the human eye due to its action on retinal photoreceptors. Its origins are closely tied to the International Commission on Illumination (CIE), which remains responsible for photometry standards and the language of light used in science and technology. When in 1931 it had become possible to model the response to light of the human eye based on reliable spectroradiometry data, the CIE published standard formulae for predicting the luminance of a stimulus. These and related colorimetry formulae are still in use, having been internationally agreed and adopted. Both fields continue to be the subject of active research and increasing accuracy. CIE S 026:2018 represents another milestone for the metrology of light (CIE, 2018a). It is the first standard where light is considered for its ability to evoke circadian and neurophysiological responses, and includes the spectral sensitivity of melanopsin-a retinal photopigment discovered, and shown to be contributing to and influencing responses from human intrinsically-photosensitive retinal ganglion cells (ipRGCs), only 20 years ago (Berson et al., 2002; Hattar et al., 2002; Provencio et al., 1998). These accessory visual functions also depend to some extent on inputs from the rods and three types of cones; until very recently, rods and cones (or "classical photoreceptors") were the only photoreceptors in visual models. If photometry standards are replaced with modern physiological data, consistent changes should be expected in the photometry of these accessory functions. This chapter outlines the current standards, their definitions and calculations, and how the main elements are related.

Dissecting and modeling photic and melanopsin effects to predict sleep disturbances induced by irregular light exposure in mice

Artificial lighting, day-length changes, shift work, and transmeridian travel all lead to sleep-wake disturbances. The nychthemeral sleep-wake cycle (SWc) is known to be controlled by output from the central circadian clock in the suprachiasmatic nuclei (SCN), which is entrained to the light-dark cycle. Additionally, via intrinsically photosensitive retinal ganglion cells containing the photopigment melanopsin (Opn4), short-term light-dark alternations exert direct and acute influences on sleep and waking. However, the extent to which longer exposures typically experienced across the 24-h day exert such an effect has never been clarified or quantified, as disentangling sustained direct light effects (SDLE) from circadian effects is difficult. Recording sleep in mice lacking a circadian pacemaker, either through transgenesis (Syt10cre/creBmal1fl/- ) or SCN lesioning and/or melanopsin-based phototransduction (Opn4-/- ), we uncovered, contrary to prevailing assumptions, that the contribution of SDLE is as important as circadian-driven input in determining SWc amplitude. Specifically, SDLE were primarily mediated (>80%) through melanopsin, of which half were then relayed through the SCN, revealing an ancillary purpose for this structure, independent of its clock function in organizing SWc. Based on these findings, we designed a model to estimate the effect of atypical light-dark cycles on SWc. This model predicted SWc amplitude in mice exposed to simulated transequatorial or transmeridian paradigms. Taken together, we demonstrate this SDLE is a crucial mechanism influencing behavior on par with the circadian system. In a broader context, these findings mandate considering SDLE, in addition to circadian drive, for coping with health consequences of atypical light exposure in our society.

Clock Gene Expression in the Eye Exhibits Circadian Oscillation and Light Responsiveness but is Not Necessary for Nocturnal Locomotor Activity of Japanese Loach, Misgurnus anguillicaudatus.

There are few model fish that are both edible and suitable for use in the laboratory. The Japanese loach (Misgurnus anguillicaudatus) is a traditional food in Japan, but is highly neglected despite its great nutritional value. To understand its circadian system and photic input pathway for synchronization of physiological activities to environmental light-dark cycles, we measured locomotor activity under light-dark and constant dark (DD) conditions. Locomotor activity was found to be higher in the nighttime than daytime, and its rhythmicity was weakened under DD conditions. The nocturnal activity of the Japanese loach is mainly controlled by environmental light, rather than the circadian clock. We explored the circadian regulation and light-responsiveness of clock gene expression in the eyes of loaches. The daily expression profiles of its mRNA revealed that most of the examined Cry and Per genes were likely regulated by internal circadian and/or environmental light signals. Among the Opsin genes transcribed in the eye, we detected the retinal photopigment porphyropsin at the protein level, which was lower than in mice. This property of loach eyes prompted us to analyze the locomotor activities of eye-enucleated fish. As a result, they still showed nocturnal circadian activity. Thus, it is likely that extraocular photoreceptive tissue(s) also contribute to the photic input pathway, although loach eyes are a circadian photosensitive tissue. This suggests that the loach mainly uses not its vision but other stimuli, such as mechanical or chemical stimuli, detected by barbels, to coordinate its nocturnal behavior.

Spontaneous color preferences in rhesus monkeys: What is the advantage of primate trichromacy?

Color perception and color signaling play an important role in various aspects of animal behavior. However, in mammals, trichromatic vision characterized by three retinal photopigments tuned to peak short, middle and long wavelengths is limited only to some primate species. In Old and New World primates a second photopigment has appeared repeatedly during phylogeny, allowing red colors to be distinguished from yellows and greens.Several hypotheses aspire to explain the adaptive benefits of trichromatic vision for primates. The predominant one is foraging adaptation for facilitation visual detection of fruits or young leaves. Alternative explanations are based on the function of red color in aposematic signaling or its role in socio-sexual communication.We tested spontaneous color preference in macaque monkeys (Macaca mulatta) for both food and non-food objects in a laboratory environment. We hypothesized that preference for or avoidance of red color together with the context of such behavior may help us to understand what the adaptive advantage leading to a rapid expansion of a gene for a second pigment in the long-wavelength region was.We found neither preference nor avoidance toward red color in non-food objects, but we found a significant preference for red color in food; therefore, we suggest that the results support the foraging hypothesis in macaque monkeys.

Demonstration of a Human Color Vision Mimic in the Infrared.

Color vision results from the interaction of retinal photopigments with reflected or transmitted visible light. The International Commission on Illumination (CIE) developed the CIE color-matching chart, which separates colors on the basis of the interaction of their spectral profiles with three retinal photopigments in the human eye. We report the development of an infrared chromaticity (CIE-IR) chart, which mimics the CIE chart, in order to discriminate between different chemicals on the basis of the interactions of their IR signatures with three different IR optical filters, instead of the retinal photopigments in the human eye. Our results demonstrate that the CIE-IR chart enables separation of different classes of chemicals, as the visible CIE chart does with color, except for those in the IR spectral region. Such results clearly show that the biomimetic sensing method based on human color vision is in fact a true analogue to color vision and that the proposed CIE-IR chart can be used as a classification method unique to this biomimetic sensing modality.

Early evolution of purple retinal pigments on Earth and implications for exoplanet biosignatures

AbstractWe propose that retinal-based phototrophy arose early in the evolution of life on Earth, profoundly impacting the development of photosynthesis and creating implications for the search for life beyond our planet. While the early evolutionary history of phototrophy is largely in the realm of the unknown, the onset of oxygenic photosynthesis in primitive cyanobacteria significantly altered the Earth's atmosphere by contributing to the rise of oxygen ~2.3 billion years ago. However, photosynthetic chlorophyll and bacterio chlorophyll pigments lack appreciable absorption at wavelengths about 500–600 nm, an energy-rich region of the solar spectrum. By contrast, simpler retinal-based light-harvesting systems such as the haloarchaeal purple membrane protein bacteriorhodopsin show a strong well-defined peak of absorbance centred at 568 nm, which is complementary to that of chlorophyll pigments. We propose a scenario where simple retinal-based light-harvesting systems like that of the purple chromoprotein bacteriorhodopsin, originally discovered in halophilic Archaea, may have dominated prior to the development of photosynthesis. We explore this hypothesis, termed the ‘Purple Earth,’ and discuss how retinal photopigments may serve as remote biosignatures for exoplanet research.

Preferences of age-0 white sturgeon for different colours and strobe rates of LED lights may inform behavioural guidance strategies

Many populations of migratory fish species, including white sturgeon (Acipenser transmontanus Richardson), are threatened due to modification of riverine systems and may experience downstream displacement or mortality at water intake structures. Efforts to reduce the impacts of these structures are beginning to incorporate behavioural guidance, where the sensory capabilities of fishes are exploited to repel them from high-risk areas or attract them towards desirable paths. Artificial lighting has been tested before, but consisted of single-spectrum lights. Using a new programmable LED-based light guidance device (LGD), we exposed age-0 white sturgeon to light strobing at 1 Hz, 20 Hz, or constant illumination with colours (green, red, blue) matching the absorbance maxima of their retinal photopigments. The behavioural responses of the sturgeon were assessed using y-maze dichotomous choice tests under both day (light) and night (dark) conditions. Sturgeon demonstrated positive phototaxis under both day and night conditions, and approached the LGD more often when light was continuous or strobing at 20 Hz compared to strobing at 1 Hz. Green light elicited the greatest rates of attraction overall. The combination of strobing and colour may help to protect imperiled fish from waterway development and serve as an effective form of mitigation at hydropower facilities and other human infrastructure where fish may be entrained or impinged.

Cone fundamentals: A model for the future of colorimetry

Cone fundamentals is the name given to the relative spectral sensitivity of long-wave sensitive, medium-wave sensitive and short-wave sensitive cones. Cone fundamentals represent the spectral absorptances of the retinal photopigments in the cones multiplied by the spectral transmittances of the ocular media through which light passes to reach the retina. The CIE 2006 cone fundamentals are based on the Stiles and Burch experimental colour matches and have been validated by recent microspectrophotometric measurements and modelling. A new physiologically based version of the MacLeod–Boynton chromaticity diagram is proposed by the CIE as well as a cone-fundamental-based ( xF, yF) chromaticity diagram. All the data necessary to use these concepts for high-precision colorimetric calculations are readily available.

Fundus autofluorescence and Photobleaching : Definitions

SummaryFundus autofluorescence (AF) imaging is a non‐invasivemethod for detection of fundus fluorophores. The 488 nm blue (short wavelength: SW) or the 787 nm near‐infrared (NIR) wavelenght are usually used to induce AF of fluorophores located in the retinal pigment epithelium (RPE). In case of excitation with SW light, the resulting AF comes predominantly from A2E located in the lipofuscin granules of the RPE. On the other hand, excitation with NIR light seems to highlight the melanin. Regardless of the type of fluorophore in the RPE, the exciting light has to pass first through the retina and especially through the photoreceptor layer. The photopigment absorbs a part of the light, which will not be transmitted to the RPE. Therefore, RPE fluorophores will be less AF. In the same time, photo‐isomerization of the 11‐cis‐retinal to 11‐trans‐retinal by the photon absorbance will be the beginning of the visual signal. Thereby, retinal photopigment loose its absorption property and the light will be easily distributed to the RPE fluorophores. This photoreceptor bleaching phenomenon could be used to better understand the origin of the hyper‐AF pattern: hyper‐AF of the RPE or lack of absorbance of signal due to photopigment loss

Isoforms of Melanopsin Mediate Different Behavioral Responses to Light

SummaryMelanopsin (OPN4) is a retinal photopigment that mediates a wide range of non-image-forming (NIF) responses to light [1, 2] including circadian entrainment [3], sleep induction [4], the pupillary light response (PLR) [5], and negative masking of locomotor behavior (the acute suppression of activity in response to light) [6]. How these diverse NIF responses can all be mediated by a single photopigment has remained a mystery. We reasoned that the alternative splicing of melanopsin could provide the basis for functionally distinct photopigments arising from a single gene. The murine melanopsin gene is indeed alternatively spliced, producing two distinct isoforms, a short (OPN4S) and a long (OPN4L) isoform, which differ only in their C terminus tails [7]. Significantly, both isoforms form fully functional photopigments [7]. Here, we show that different isoforms of OPN4 mediate different behavioral responses to light. By using RNAi-mediated silencing of each isoform in vivo, we demonstrated that the short isoform (OPN4S) mediates light-induced pupillary constriction, the long isoform (OPN4L) regulates negative masking, and both isoforms contribute to phase-shifting circadian rhythms of locomotor behavior and light-mediated sleep induction. These findings demonstrate that splice variants of a single receptor gene can regulate strikingly different behaviors.

Colour Vision Revisited

Congenital red-green colour deficiency is an X-linked inherited disorder more frequently encountered in males compared to females. Screening of coour deficiency is crucial in various occupations, at times to safeguard colour deficient individual as well as vulnerable population. Acquired colour deficiency is seen in multiple inherited retinal photopigment disorders, vascular retonopathies and optic nerve disorders. Multiple tests have been devised to detect, classify and grade colour deficiency, each having a specific purpose. Tinted spectacles and contact lenses have been tried to rehabilitate colour deficient individuals with limited success.

The role of intrinsically photosensitive retinal ganglion cells in nonimage-forming responses to light.

Light exerts many effects on behavior and physiology. These effects can be characterized as either image-forming or nonimage-forming (NIF) visual processes. Image-forming vision refers to the process of detecting objects and organisms in the environment and distinguishing their physical characteristics, such as size, shape, and direction of motion. NIF vision, in contrast, refers to effects of light that are independent of fine spatiotemporal vision. NIF effects are many and varied, ranging from modulation of basal physiology, such as heart rate and body temperature, to changes in higher functions, such as mood and cognitive performance. In mammals, many NIF effects of light are dependent upon the inner retinal photopigment melanopsin and the cells in which melanopsin is expressed, the intrinsically photosensitive retinal ganglion cells (ipRGCs). The ipRGCs project broadly throughout the brain. Many of these projections terminate in areas known to mediate NIF effects, while others terminate in regions whose link to photoreception remains to be established. Additionally, the presence of ipRGC projections to areas of the brain with no known link to photoreception suggests the existence of additional ipRGC-mediated NIF effects. This review summarizes the known NIF effects of light and the role of melanopsin and ipRGCs in driving these effects, with an eye toward stimulating further investigation of the many and varied effects of light on physiology and behavior.

Activation Changes in Zebra Finch (Taeniopygia guttata) Brain Areas Evoked by Alterations of the Earth Magnetic Field

Many animals are able to perceive the earth magnetic field and to use it for orientation and navigation within the environment. The mechanisms underlying the perception and processing of magnetic field information within the brain have been thoroughly studied, especially in birds, but are still obscure. Three hypotheses are currently discussed, dealing with ferromagnetic particles in the beak of birds, with the same sort of particles within the lagena organs, or describing magnetically influenced radical-pair processes within retinal photopigments. Each hypothesis is related to a well-known sensory organ and claims parallel processing of magnetic field information with somatosensory, vestibular and visual input, respectively. Changes in activation within nuclei of the respective sensory systems have been shown previously. Most of these previous experiments employed intensity enhanced magnetic stimuli or lesions. We here exposed unrestrained zebra finches to either a stationary or a rotating magnetic field of the local intensity and inclination. C-Fos was used as an activity marker to examine whether the two treatments led to differences in fourteen brain areas including nuclei of the somatosensory, vestibular and visual system. An ANOVA revealed an overall effect of treatment, indicating that the magnetic field change was perceived by the birds. While the differences were too small to be significant in most areas, a significant enhancement of activation by the rotating stimulus was found in a hippocampal subdivision. Part of the hyperpallium showed a strong, nearly significant, increase. Our results are compatible with previous studies demonstrating an involvement of at least three different sensory systems in earth magnetic field perception and suggest that these systems, probably less elaborated, may also be found in nonmigrating birds.

Glare's Causes, Consequences, and Clinical Challenges After a Century of Ophthalmic Study

To provide a multidisciplinary synthesis of scientific information on disability, discomfort, dazzling, and scotomatic (photostress) glare. Perspective. Analysis and integration of relevant historical and contemporary publications on glare in ophthalmology, illumination engineering, neurology, and other relevant disciplines. Disability glare is caused by scattered intraocular light (straylight) not useful for vision. Straylight casts a veiling luminance on the retina, reducing image contrast and impairing vision. In common environments, glare and target illumination sources have the same or similar spectra. Colored spectacle or intraocular lens filters reduce both proportionately, so they do not increase retinal image contrast or decrease disability glare. Discomfort glare is caused by situational illumination too intense or variable. Dazzling glare occurs when high illuminances are spread across the retina. Neurophysiological research is clarifying how discomfort and dazzling glare depend on different retinal photoreceptors and nociceptive brain pathways involving the trigeminal ganglion and thalamus. Photostress is caused by excessive local retinal photopigment bleaching uncommon in ordinary situations. Optical glare countermeasures are available for daytime driving but not oncoming automobile headlights at night. Filters that decrease daytime discomfort or dazzling glare also reduce nighttime mesopic and scotopic sensitivity. Glare is problematic for patients and clinicians despite a century of scientific research. Advances in understanding glare have been hampered by its complex, multidisciplinary nature and limited interdisciplinary communication. We provide one pathway through the forest of glare nomenclature and mechanisms. Improved diagnostic and therapeutic methodologies await continuing progress in understanding glare.

Melanopsin as a Sleep Modulator: Circadian Gating of the Direct Effects of Light on Sleep and Altered Sleep Homeostasis in Opn4−/− Mice

Author SummaryLight affects sleep in two ways: indirectly through the phase adjustment of circadian rhythms and directly through nonvisual mechanisms that are independent of the circadian system. The direct effects of light include the promotion of sleep in night-active animals and of alertness in diurnal species. We analyzed sleep and the electroencephalogram (EEG) under various light–dark regimens in mice lacking melanopsin (Opn4 −/−), a retinal photopigment crucial for conveying light-level information to the brain, to determine the role of melanopsin, as opposed to rod and cones, in mediating these direct effects of light. We show that melanopsin mediates the direct effects of light during the subjective dark period, whereas rods and cones contribute to these effects in the light period. Our finding that “sleep-active” (i.e., galanin-positive) neurons of the anterior hypothalamus are not activated by light in Opn4 −/− mice suggests that these neurons are part of the circuitry whereby light promotes sleep. Also, the alerting effects of transitions into darkness were less pronounced in Opn4 −/− mice judged on the reduced increase in EEG theta and gamma activity. Finally, and unexpectedly, the rate at which the need for sleep, quantified as EEG delta power, accumulated during wakefulness was found to be reduced in Opn4 −/− mice both during baseline and sleep deprivation conditions, implicating a photopigment in the homeostatic regulation of sleep. We conclude that melanopsin contributes to the direct effects of light and darkness, and in interaction with circadian and homeostatic drive, determines the occurrence and quality of both sleep and waking. If confirmed in humans, our observations will have applications for the clinical use of light as well as for societal lighting conditions.

Evolutionary models of color categorization II Realistic observer models and population heterogeneity

The evolution of color categorization is investigated using computer simulations of agent population categorization games. Various realistic observer types are implemented based on Farnsworth-Munsell 100 Hue Test human performance data from normal and anomalous trichromats, dichromats, and humans with four retinal photopigments. Results show that (i) a small percentage of realistically modeled deficient agents greatly affects the shared categorization solutions of the entire population in terms of color category boundary locations; (ii) for realistically modeled populations, dichromats have the strongest influence on the color categorization; their characteristic forms of color confusion affect (i.e., attract or repel) color boundary locations and accord with our findings for homogeneous dichromat populations [J. Opt. Soc. Am. A26, 1414-1423 (2009)]; (iii) adding anomalous trichromats or trichromat "experts" does not destabilize the solutions or substantially alter solution structure. The results provide insights regarding the mechanisms that may constrain universal tendencies in human color categorization systems.

Daily Profile in Melanopsin Transcripts Depends on Seasonal Lighting Conditions in the Rat Retina

The retinal photopigment melanopsin (Opn4) mediates photoentrainment of the circadian system. In the present study, seasonal regulation of the melanopsin gene was investigated in comparison with the arylalkylamine N-acetyltransferase (AA-NAT) gene as an indicator of retinal pacemaker output. For this purpose, the daily profiles in the amount of melanopsin mRNA and AA-NAT mRNA were monitored under 8 : 16 h light/dark, 12 : 12 h light/dark and 16 : 8 h light/dark photoperiods using real-time polymerase chain reaction analysis. We found that, under all of the lighting regimes, melanopsin and AA-NAT expression oscillated with a peak around dark onset and the middle of the dark phase, respectively. The lighting regime influenced both genes, but in an opposing manner. Under long photoperiods, the duration of peak expression was prolonged for melanopsin, whereas it was shortened for AA-NAT. Under constant darkness, the rhythm of mRNA was abolished for melanopsin, but persisted for AA-NAT whereas, under constant light, the rhythm of mRNA was abolished for both genes. Our findings suggest that, in contrast to the AA-NAT gene, the daily and photoperiod-dependent regulation of the melanopsin gene does not rely on a circadian oscillator but is directly illumination-dependent.

Melanopsin in cells of origin of the retinohypothalamic tract.

All known eukaryotic organisms exhibit physiological and behavioral rhythms termed circadian rhythms that cycle with a near-24-hour period; in mammals, light is the most potent stimulus for entraining endogenous rhythms to the daily light cycle. Photic information is transmitted via the retinohypothalamic tract (RHT) to the suprachiasmatic nucleus (SCN) in the hypothalamus, where circadian rhythms are generated, but the retinal photopigment that mediates circadian entrainment has remained elusive. Here we show that most retinal ganglion cells (RGCs) that project to the SCN express the photopigment melanopsin.