Differences In Light Sensitivity Research Articles

Greater sensitivity of the circadian system of women to bright light, but not dim‐to‐moderate light

AbstractWomen typically sleep and wake earlier than men and have been shown to have earlier circadian timing relative to the light/dark cycle that synchronizes the clock. A potential mechanism for earlier timing in women is an altered response of the circadian system to evening light. We characterized individual‐level dose–response curves for light‐induced melatonin suppression using a within‐subjects protocol. Fifty‐six participants (29 women, 27 men; aged 18–30 years) were exposed to a range of light illuminances (10, 30, 50, 100, 200, 400, and 2000 lux) using melatonin suppression relative to a dim control (<1 lux) as a marker of light sensitivity. Women were free from hormonal contraception. To examine the potential influence of sex hormones, estradiol and progesterone was examined in women and testosterone was examined in a subset of men. Menstrual phase was monitored using self‐reports and estradiol and progesterone levels. Women exhibited significantly greater melatonin suppression than men under the 400‐lux and 2000‐lux conditions, but not under lower light conditions (10–200 lux). Light sensitivity did not differ by menstrual phase, nor was it associated with levels of estradiol, progesterone, or testosterone, suggesting the sex differences in light sensitivity were not acutely driven by circulating levels of sex hormones. These results suggest that sex differences in circadian timing are not due to differences in the response to dim/moderate light exposures typically experienced in the evening. The finding of increased bright light sensitivity in women suggests that sex differences in circadian timing could plausibly instead be driven by a greater sensitivity to phase‐advancing effects of bright morning light.

Light on Shedding: A Review of Sex and Menstrual Cycle Differences in the Physiological Effects of Light in Humans.

The human circadian system responds to light as low as 30 photopic lux. Furthermore, recent evidence shows that there are huge individual differences in light sensitivity, which may help to explain why some people are more susceptible to sleep and circadian disruption than others. The biological mechanisms underlying the differences in light sensitivity remain largely unknown. A key variable of interest in understanding these individual differences in light sensitivity is biological sex. It is possible that in humans, males and females differ in their sensitivity to light, but the evidence is inconclusive. This is in part due to the historic exclusion of women in biomedical research. Hormonal fluctuations across the menstrual cycle in women has often been cited as a confound by researchers. Attitudes, however, are changing with funding and publication agencies advocating for more inclusive research frameworks and mandating that women and minorities participate in scientific research studies. In this article, we distill the existing knowledge regarding the relationship between light and the menstrual cycle. There is some evidence of a relationship between light and the menstrual cycle, but the nature of this relationship seems dependent on the timing of the light source (sunlight, moonlight, and electric light at night). Light sensitivity may be influenced by biological sex and menstrual phase but there might not be any effect at all. To better understand the relationship between light, the circadian system, and the menstrual cycle, future research needs to be designed thoughtfully, conducted rigorously, and reported transparently.

Patches of Dysflective Cones in Eyes With No Known Disease.

PurposeTo characterize the structure and function of patches of dysflective cones in the foveal region of subjects with normal vision and no known pathology. Dysflective cones are cones that have little or no reflective properties in optical coherence tomography (OCT) or adaptive optics scanning laser ophthalmoscope (AOSLO) images yet exhibit measurable function.MethodsAOSLO images were surveyed for the presence of hyporeflective cone patches, and subjects were brought back for imaging to determine the changes in the hyporeflective region. Adaptive optics microperimetry (AOMP) was used to assess the function of hyporeflective patches in four subjects to determine that they did, in fact, contain dysflective cones. AOMP utilized a stimulus size of less than 1 arcmin to measure thresholds inside and outside the hyporeflective region.ResultsNineteen out of 47 individuals retrospectively reviewed had one or more regions with hyporeflective cone patches in one or both eyes. Ten subjects with hyporeflective cone patches were brought back for imaging. Seven of the 10 had resolved at follow up, and in three subjects new hyporeflective patches appeared in a different location. All AOMP-measured subjects had measurable function in the dysflective cone region. Three out of four subjects showed no difference in light sensitivity in the dysflective region compared to adjacent areas, and one subject showed a 3× reduction in sensitivity in the area.ConclusionsPatches of dysflective cone have been identified in subjects with normal vision and no known pathology, and we have observed instances where dysflective cones in these subjects regain normal reflective properties.

Melatonin, circadian rhythms and glaucoma: current perspective.

Primary open-angle glaucoma as a causal factor for circadian disruption: Living by the clock, in alignment with external time cues is an important condition for human health and well-being. Periodic changes in the ambient light serve as a key factor to synchronize the endogenously generated circadian rhythms. The retina perceives the photic signals and transmits them to the central body clock, the suprachiasmatic nuclei (SCN), via the retinohypothalamic tract. Primary open angle glaucoma (POAG) is an optic neuropathy, in which disease progression can be monitored by assessing damage to the retinal ganglion cells (RGCs) (Pérez-Rico et al., 2010; Feigl et al., 2011; Kankipati et al., 2011). Damage of retinal ganglion cells, particularly of intrinsically photosensitive RGCs (ipRGCs), is also one of the causes of circadian disruption. Pathophysiological mechanisms of POAG are complex, including elevated intraocular pressure (IOP), which adds mechanical stress, causing damage, dysfunction, and death of the RGCs (Figure 1). Glaucoma progression affects both image-forming and non-image-forming visual functions of RGCs. A central role of ipRGCs is to convey non-image-forming photic information to the clock. Their damage reduces light signaling to the SCN. Already in early stages of glaucoma, ipRGCs are dysfunctional (Pérez-Rico et al., 2010; Feigl et al., 2011; Kankipati et al., 2011).Figure 1: Melatonin potential to counteract complex circadian alterations with aging, neurodegeneration, specifically in glaucoma.ipRGCs: Intrinsically photosensitive retinal ganglion cells; SNPs: single nucleotide polymorphisms.As RGCs are progressively altered, and non-image-forming function is affected, circadian rhythms are disrupted, sleep is impaired, and mood is altered (Graticelli et al., 2015; Gubin et al., 2019, 2021). Circadian rhythm alterations are found in POAG as compared to age-matched healthy peers (Gubin et al., 2019). Circadian disruption worsens in advanced POAG (Gubin et al., 2019, Neroev et al., 2020), correlating to the increasing loss of ipRGCs with disease progression (Obara et al., 2016). Circadian rhythms also change with increasing age. Age-dependent circadian alterations are not necessarily related to retinal damage, as photic transduction to the central clock is not always compromised. When they are related to retinal damage, they can be due to either neurodegenerative ipRGCs damage, or to ipRGC damage caused by increased mean or deregulated circadian IOP. The intriguing principal difference between the presence or absence of retinal damage in aging is that the reduced light transmitted to the SCN by damaged ipRGCs phase-delays circadian rhythms, but ipRGC-uncompromised aging is commonly associated with phase-advanced circadian rhythms (Gubin et al., 2019). Since individual differences in sensitivity to light, and/or in endogenous melatonin production may interfere with this theoretical modeling, the search for specific genetic factors that may determine such individual differences constitutes a promising approach. In conditions where photic entrainment is compromised, not only is the alignment with external time cues altered, so can be the variability of overt physiologic functions. We showed that large inter-individual variability obscured the circadian IOP rhythm in POAG (Neroev et al., 2020). Circadian IOP rhythms had specific alterations manifested in advanced, but not in mild POAG, which were associated with the progressive damage and dysfunction of RGCs. In patients with RGCs’ global loss volume above 15%, as assessed by high-definition optical coherence tomography, the 24-hour IOP rhythm peaked during the night, whereas in patients with stable POAG and a two-eye mean RGCs’ global loss volume less than 10%, the IOP peaked predominantly during the daytime. Misalignment between circadian rhythms in body temperature and IOP increased as a function of global loss volume loss. Higher nocturnal IOP in POAG may adversely affect the disease state, fostering damage to RGCs (Neroev et al., 2020). Depending on individual genetic factors, these changes may manifest themselves to a different degree. Individual clock properties depend on numerous genetic factors, comprising clock genes and melatonin receptor genes, melatonin nuclear receptor 1b (MTNR1b) in particular, which may account for large individual differences in light sensitivity. Our pilot study of gene polymorphisms in POAG showed that the D-allele of the Angiotensin-converting enzyme holding a deletion of the 16th intron Alu repeat was significantly associated with alterations of the circadian IOP rhythm. It may also account for the resistance to IOP-lowering therapy (Neroev et al., 2020). Endogenous melatonin production in primary open-angle glaucoma: Glaucoma patients experienced reduced post-illumination pupil response (Kankipati et al., 2011) and reduced nocturnal melatonin suppression by light (Pérez-Rico et al., 2010). Clinical evidence for changes in the timing and mean values of endogenous melatonin production in POAG was also evident (reviewed in Gubin et al., 2021): in POAG, salivary melatonin can be lower than in age-matched controls without POAG; even greater alterations were observed In advanced stages of the disease. The main alteration concerned the time of maximal secretion of melatonin. Such altered melatonin production in POAG and other neurodegenerative pathologies can stem from different factors, including diminished light signaling due to a reduced sensitivity to light. The presence of certain gene polymorphisms can increase the susceptibility of carriers to these factors. We investigated 24-hour profiles of salivary melatonin under controlled lighting conditions and analyzed several clock genes and polymorphisms of the melatonin receptor gene MTNR1b (Gubin et al., 2021). Patients diagnosed with stable POAG had unaltered circadian rhythms of salivary melatonin and body temperature, which peaked at the anticipated time. Circadian rhythms of both variables were delayed, however, in patients diagnosed with advanced POAG (Gubin et al., 2019, 2021). Their 24-hour mean value and circadian amplitude of melatonin were also reduced (Gubin et al., 2021). Analysis of selected polymorphisms in clock and melatonin receptor genes revealed that these changes were observed specifically in carriers of the MTNR1B rs10830963 G-allele with advanced POAG. Overt changes of circadian phenotypes in POAG patients occur when several factors are present in combination: for example, when RGC loss exceeds a certain threshold in carriers of those genotypes, known to be associated with a prolonged duration of melatonin production. The MTNR1B rs10830963 G-allele is mainly known for its association with an elevated fasting glucose and the risk of type 2 diabetes, but it is also listed as a factor predicting POAG independently of diabetes (Shen et al., 2016), a fact supporting the assumption that melatonin may have pleiotropic physiological functions in the development of POAG. Melatonin to counteract non-image-forming visual function deterioration in primary open-angle glaucoma: To enhance circadian entrainment, morning light therapy and evening melatonin administration can both be effective. While studies aimed at estimating the merit of morning light therapy or outdoor light exposure in POAG are lacking, some studies provide evidence for a beneficial effect of exogenously administered melatonin in glaucoma and neurodegenerative pathologies (González Fleitas et al., 2021; Gubin et al., 2021). Melatonin transmits environmental light signals, thus facilitating the synchronization of peripheral clocks. It can thus mitigate several conditions such as glaucoma and its progression: disruption of circadian rhythms, compromised sleep, and mood (Tosini et al., 2012; Gubin et al., 2021) (Figure 1). Melatonin improves internal synchronization, ameliorating circadian alignment between local (IOP) and systemic (temperature) circadian rhythms (Gubin et al., 2021), which were progressively desynchronized with greater RGCs loss in POAG (Neroev et al., 2020). Melatonin is produced endogenously with a pronounced 24-hour rhythm governed by the SCN. Peak production occurs at night. Its specific timing may differ among individuals. Exact endogenous factors that predetermine these differences are not known but may include single nucleotide polymorphisms within candidate genes or melatonin receptors that influence sensitivity to light. Melatonin receptors (MTNR1B) are widespread in numerous brain regions. Their structure may determine the specific response to (both endogenous and exogenous) melatonin. We investigated the effect of oral melatonin administration (daily at 10:30 p.m. for 90 days) on the circadian rhythms of IOP, body temperature, and the pattern electroretinogram in patients diagnosed with stable or advanced POAG, also assessing effects on sleep and mood (Gubin et al., 2021). Melatonin administration increased the stability of the circadian body temperature rhythm, improving its alignment with the circadian IOP rhythm. Melatonin decreased IOP to a different extent at different times of the day and decreased the standard deviation of IOP with statistical significance. Larger changes were found in patients with initially higher 24-hour mean values of IOP. Melatonin improved RGCs function in patients with advanced POAG by increasing the amplitude of pattern electroretinogram that correlated positively with the degree of RGCs loss. Melatonin had more pronounced positive effects on sleep and mood in patients with advanced POAG, who had greater damage of their RGCs. Taken together melatonin has the potential to restore disrupted circadian rhythms in POAG. Its systemic effect is distinct from its local effect on the retinal circadian rhythms. Similar to light exposure, physiological effects of melatonin depend on the time of its administration. Personalizing melatonin administration in terms of its timing and dosing, accounting for the genetic profile, is expected to further refine its multiple benefits. Melatonin may provide beneficial effects in POAG stemming from both its ability to reduce IOP and its potential to prevent RGC damage derived from mechanisms of neurodegeneration (Hardeland, 2021) (Figure 1). These effects may not only mitigate circadian disruption but also improve other aspects of health and well-being. Circadian alignment may strengthen human physiological functions and help slow neurodegeneration. The choice of an optimal melatonin dosing, however, is not yet clear (Hardeland, 2021). Consideration of the best timing should be based on internal circadian parameters and on genes that may account for personal differences in melatonin efficacy. Concluding remarks: In assessing disruptions in the non-image-forming visual system in POAG patients, one needs to discriminate between different situations. There may be complex, non-specific changes in circadian rhythms with age. Changes related to neurogenerative disease, including Alzheimer’s disease, Parkinson’s disease, and POAG, might promote alterations in neural structures: SCN, pineal, retina. Changes specific to POAG include additional RGC damage caused by the elevated IOP, together with abnormal circadian patterns of physiological variables such as IOP, body temperature, pattern electroretinogram, and melatonin (Figure 1). The circadian IOP pattern with relatively higher values during the resting span may foster harmful effects of IOP on RGCs, since tissue sensitivity may vary depending on circadian time (Neroev et al., 2020). Numerous candidate gene polymorphisms may play a role, alone or in combination with others, affecting the susceptibility to POAG itself (as a primary pathology of vision), or POAG-associated alterations of circadian rhythms, sleep, and mood, linked to non-visual pathways. To answer this question, clinical data combined with circadian profiles of melatonin and other physiological variables, chronotype questionnaires, sleep and mood information, to be checked against single nucleotide polymorphisms databases, should be collected on large cohorts. Constructive collaboration among ophthalmologists, chronobiologists, and geneticists is therefore advocated. The present work was supported by the Russian Foundation for Basic Research (grant No. 19-015-00329) (to DG), and by Government of Tyumen District, Decree of 20.11.2020 No. 928-rp (to DG). The authors have no proprietary or commercial interest in any materials discussed in this article.

Considerations on how to light the night-shift

Electric lighting has decreased dependence on natural light to illuminate the workplace. Humans are genetically predisposed to be day-oriented (diurnal) and depend on daylight to regulate circadian rhythms. Shift work will force workers to sleep and work at non-biological times, inducing circadian disruption with implications for workers’ safety and health. The scientific literature may be used in practice in shift work settings to improve safety, performance and health in the workplace by reducing circadian misalignment. Alertness profiles at work and degree of melatonin suppression may indicate degree of circadian disruption among workers. However, when considering lighting solutions at night, there are several factors that need consideration. Light measures based on biological effectiveness should be used rather than room illuminance giving better predictions of performance and long-term health among workers. Also, large individual differences in light sensitivity and preferences suggest not only to rely on common lighting alone but also to implement complementary individual lighting solutions at work. Lighting advice should consider shift scheduling characteristics such as speed of turnover and shift timing to guide decisions of preferred circadian phase influence. Lighting should also include the flexibility to be fit for morning, afternoon and evening work.

The Role of Light Sensitivity and Intrinsic Circadian Period in Predicting Individual Circadian Timing.

There is large interindividual variability in circadian timing, which is underestimated by mathematical models of the circadian clock. Interindividual differences in timing have traditionally been modeled by changing the intrinsic circadian period, but recent findings reveal an additional potential source of variability: large interindividual differences in light sensitivity. Using an established model of the human circadian clock with real-world light recordings, we investigated whether changes in light sensitivity parameters or intrinsic circadian period could capture variability in circadian timing between and within individuals. Healthy participants (n = 12, aged 18-26 years) underwent continuous light monitoring for 3 weeks (Actiwatch Spectrum). Salivary dim-light melatonin onset (DLMO) was measured each week. Using the recorded light patterns, a sensitivity analysis for predicted DLMO times was performed, varying 3 model parameters within physiological ranges: (1) a parameter determining the steepness of the dose-response curve to light (p), (2) a parameter determining the shape of the phase-response curve to light (K), and (3) the intrinsic circadian period (tau). These parameters were then fitted to obtain optimal predictions of the three DLMO times for each individual. The sensitivity analysis showed that the range of variation in the average predicted DLMO times across participants was 0.65 h for p, 4.28 h for K, and 3.26 h for tau. The default model predicted the DLMO times with a mean absolute error of 1.02 h, whereas fitting all 3 parameters reduced the mean absolute error to 0.28 h. Fitting the parameters independently, we found mean absolute errors of 0.83 h for p, 0.53 h for K, and 0.42 h for tau. Fitting p and K together reduced the mean absolute error to 0.44 h. Light sensitivity parameters captured similar variability in phase compared with intrinsic circadian period, indicating they are viable targets for individualizing circadian phase predictions. Future prospective work is needed that uses measures of light sensitivity to validate this approach.

Individual differences in light sensitivity affect sleep and circadian rhythms.

Artificial lighting is omnipresent in contemporary society with disruptive consequences for human sleep and circadian rhythms because of overexposure to light, particularly in the evening/night hours. Recent evidence shows large individual variations in circadian photosensitivity, such as melatonin suppression, due to artificial light exposure. Despite the emerging body of research indicating that the effects of light on sleep and circadian rhythms vary dramatically across individuals, recommendations for appropriate light exposure in real-life settings rarely consider such individual effects. This review addresses recently identified links among individual traits, for example, age, sex, chronotype, genetic haplotypes, and the effects of evening/night light on sleep and circadian hallmarks, based on human laboratory and field studies. Target biological mechanisms for individual differences in light sensitivity include differences occurring within the retina and downstream, such as the central circadian clock. This review also highlights that there are wide gaps of uncertainty, despite the growing awareness that individual differences shape the effects of evening/night light on sleep and circadian physiology. These include (1) why do certain individual traits differentially affect the influence of light on sleep and circadian rhythms; (2) what is the translational value of individual differences in light sensitivity in populations typically exposed to light at night, such as night shift workers; and (3) what is the magnitude of individual differences in light sensitivity in population-based studies? Collectively, the current findings provide strong support for considering individual differences when defining optimal lighting specifications, thus allowing for personalized lighting solutions that promote quality of life and health.

Pinopsin and photoreception in the pineal organ of the domestic turkey during post-hatching development

The avian pineal organ is photosensitive because of the presence of photopigments, of which pinopsin seems to be one of the most important. This organ is subject to far-reaching changes during post-hatching development, but evidence regarding pinopsin presence and direct photoreception during this time is lacking. This study was carried out to demonstrate the following: 1) the structures showing immunoreactivity to pinopsin in the turkey pineal organ, 2) the changes of these structures during development, 3) the pinopsin localization in pinealocytes in monolayer cultures, and 4) the role of direct photoreception in the regulation of melatonin secretion in pineal organs in adult turkeys. Pinopsin immunoreactivity was localized in the apical extensions of columnar cells limiting the follicular lumen, in fiber-like structures located between columnar cells in the inner part of follicle wall, in string-shapes or small spherical structures distributed in the outer part of follicle wall and in amorphous material inside the follicle lumen. In young birds, immunoreactivity was also sporadically noted in cell bodies of rudimentary receptor pinealocytes. The distribution of pinopsin showed prominent age-dependent changes, including a subsequent increase in pinopsin-positive structures in the outer part of the follicle wall and a prominent reduction in the number and size of positive apical extensions in 40- and 56-week-old turkeys. These data demonstrate that the role of secretory pinealocytes in pineal photoreception increases with age. In monolayer cultures, all pinealocytes showed strong reactions in club- or bulbous-shaped prolongations. The pineal organs of adult birds were less sensitive to light exposition at night than those of young turkeys, which points to differences in light sensitivity between rudimentary receptor and secretory pinealocytes. However, direct photoreception could play an important role in the regulation of melatonin secretion in adult turkeys.

Traits related to bipolar disorder are associated with an increased post-illumination pupil response

Mood states in bipolar disorder appear to be closely linked to changes in sleep and circadian function. It has been suggested that hypersensitivity of the circadian system to light may be a trait vulnerability for bipolar disorder. Healthy persons with emotional-behavioural traits associated with bipolar disorder also appear to exhibit problems with circadian rhythms, which may be associated with individual differences in light sensitivity. This study investigated the melanopsin-driven post-illumination pupil response (PIPR) in relation to emotional-behavioural traits associated with bipolar disorder (measured with the General Behavior Inventory) in a non-clinical group (n = 61). An increased PIPR was associated with increased bipolar disorder-related traits. Specifically, the hypomania scale of the General Behavior Inventory was associated with an increased post-blue PIPR. Further, both the full hypomania and shortened ‘7 Up’ scales were significantly predicted by PIPR, after age, sex and depressive traits were controlled. These findings suggest that increased sensitivity to light may be a risk factor for mood problems in the general population, and support the idea that hypersensitivity to light is a trait vulnerability for, rather than symptom of, bipolar disorder.

Determination of the Acceptable Ambient Light Exposure during Drug Product Manufacturing for Long-Term Stability of Monoclonal Antibodies.

Monoclonal antibodies (mAbs) are exposed to light during drug product (DP) manufacturing, and the acceptable levels of light exposure needs to be determined based on the impact on product quality. In this study, a mild and more representative light model consisting of ambient light instead of stress light as prescribed by ICH Q1B was used to evaluate the impact of light exposure on mAb DP quality. The immediate effect of ambient light exposure on protein DP quality was determined to be dependent on the amount of light exposure rather than light intensity (up to 5000 lux). The impact on quality of mAbs is product specific due to their differences in light sensitivity, in which mAb II shows larger increases in IEC basic variants and larger decreases in SEC monomer when compared to mAb I after 0.24 million lux hours of light exposure. The acceptable ambient light exposure for mAb II DP manufacturing was determined to be 0.13 million lux hours, in which no impact on product quality was observed after the short-term light exposure. Additionally, real-time storage (5 °C) of the DP after the prescribed ambient light exposure showed no impact to various product quality attributes. The light model used in this study is capable of determining the acceptable amount of ambient light exposure for mAbs, especially during DP manufacturing processes.

Sex differences in light sensitivity impact on brightness perception, vigilant attention and sleep in humans

Artificial light endows a “round-the-clock”, 24-h/7-d society. Chronic exposure to light at night contributes to health hazards for humans, including disorders of sleep. Yet the influence of inter-individual traits, such as sex-differences, on light sensitivity remains to be established. Here we investigated potential sex-differences to evening light exposure of 40 lx at 6500 K (blue-enriched) or at 2500 K (non-blue-enriched), and their impact on brightness perception, vigilant attention and sleep physiology. In contrast to women, men had higher brightness perception and faster reaction times in a sustained attention task during blue-enriched light than non-blue-enriched. After blue-enriched light exposure, men had significantly higher all-night frontal NREM sleep slow-wave activity (SWA: 2–4 Hz), than women, particularly during the beginning of the sleep episode. Furthermore, brightness perception during blue-enriched light significantly predicted men’s improved sustained attention performance and increased frontal NREM SWA. Our data indicate that, in contrast to women, men show a stronger response to blue-enriched light in the late evening even at very low light levels (40lux), as indexed by increased vigilant attention and sleep EEG hallmarks. Collectively, the data indicate that sex differences in light sensitivity might play a key role for ensuring the success of individually-targeted light interventions.

An ancestral haplotype of the human PERIOD2 gene associates with reduced sensitivity to light-induced melatonin suppression.

Humans show various responses to the environmental stimulus in individual levels as “physiological variations.” However, it has been unclear if these are caused by genetic variations. In this study, we examined the association between the physiological variation of response to light-stimulus and genetic polymorphisms. We collected physiological data from 43 subjects, including light-induced melatonin suppression, and performed haplotype analyses on the clock genes, PER2 and PER3, exhibiting geographical differentiation of allele frequencies. Among the haplotypes of PER3, no significant difference in light sensitivity was found. However, three common haplotypes of PER2 accounted for more than 96% of the chromosomes in subjects, and 1 of those 3 had a significantly low-sensitive response to light-stimulus (P < 0.05). The homozygote of the low-sensitive PER2 haplotype showed significantly lower percentages of melatonin suppression (P < 0.05), and the heterozygotes of the haplotypes varied their ratios, indicating that the physiological variation for light-sensitivity is evidently related to the PER2 polymorphism. Compared with global haplotype frequencies, the haplotype with a low-sensitive response was more frequent in Africans than in non-Africans, and came to the root in the phylogenetic tree, suggesting that the low light-sensitive haplotype is the ancestral type, whereas the other haplotypes with high sensitivity to light are the derived types. Hence, we speculate that the high light-sensitive haplotypes have spread throughout the world after the Out-of-Africa migration of modern humans.

Light-sensitive brain pathways and aging.

Notwithstanding its effects on the classical visual system allowing image formation, light acts upon several non-image-forming (NIF) functions including body temperature, hormonal secretions, sleep-wake cycle, alertness, and cognitive performance. Studies have shown that NIF functions are maximally sensitive to blue wavelengths (460–480 nm), in comparison to longer light wavelengths. Higher blue light sensitivity has been reported for melatonin suppression, pupillary constriction, vigilance, and performance improvement but also for modulation of cognitive brain functions. Studies investigating acute stimulating effects of light on brain activity during the execution of cognitive tasks have suggested that brain activations progress from subcortical regions involved in alertness, such as the thalamus, the hypothalamus, and the brainstem, before reaching cortical regions associated with the ongoing task. In the course of aging, lower blue light sensitivity of some NIF functions has been reported. Here, we first describe neural pathways underlying effects of light on NIF functions and we discuss eye and cerebral mechanisms associated with aging which may affect NIF light sensitivity. Thereafter, we report results of investigations on pupillary constriction and cognitive brain sensitivity to light in the course of aging. Whereas the impact of light on cognitive brain responses appears to decrease substantially, pupillary constriction seems to remain more intact over the lifespan. Altogether, these results demonstrate that aging research should take into account the diversity of the pathways underlying the effects of light on specific NIF functions which may explain their differences in light sensitivity.

Benchmarking of optical dimerizer systems.

Optical dimerizers are a powerful new class of optogenetic tools that allow light-inducible control of protein–protein interactions. Such tools have been useful for regulating cellular pathways and processes with high spatiotemporal resolution in live cells, and a growing number of dimerizer systems are available. As these systems have been characterized by different groups using different methods, it has been difficult for users to compare their properties. Here, we set about to systematically benchmark the properties of four optical dimerizer systems, CRY2/CIB1, TULIPs, phyB/PIF3, and phyB/PIF6. Using a yeast transcriptional assay, we find significant differences in light sensitivity and fold-activation levels between the red light regulated systems but similar responses between the CRY2/CIB and TULIP systems. Further comparison of the ability of the CRY2/CIB1 and TULIP systems to regulate a yeast MAPK signaling pathway also showed similar responses, with slightly less background activity in the dark observed with CRY2/CIB. In the process of developing this work, we also generated an improved blue-light-regulated transcriptional system using CRY2/CIB in yeast. In addition, we demonstrate successful application of the CRY2/CIB dimerizers using a membrane-tethered CRY2, which may allow for better local control of protein interactions. Taken together, this work allows for a better understanding of the capacities of these different dimerization systems and demonstrates new uses of these dimerizers to control signaling and transcription in yeast.

Male but not female Wistar rats show increased anxiety-like behaviour in response to bright light in the defensive withdrawal test

The defensive withdrawal test (DWT) is used to model anxiety-like behaviour in rats. The aim of this study was to investigate whether an aversive stimulus, bright light, affects the behaviour in this test. Additionally, the effect of habituation to the apparatus was studied. Both male and female Wistar rats were used to study whether sex differences exist in the DWT, as reported for other tests of anxiety. On day 1 half of the rats were tested under low light and half under bright light. Two to seven days after trial one the same rats were repeatedly tested under the same light condition for five consecutive days. The male rats showed a higher degree of anxiety-like behaviour when tested under bright light than under low light. In contrast, the behaviour of the female rats was not affected by changes in illumination. Male rats also exhibited elevated anxiety-like behaviour compared to female rats under bright light, whereas under low light conditions no sex difference was seen. Males in low light habituated much faster than males tested under bright light, whereas in females there was little difference in habituation between low and bright light. In summary, we found that bright light is aversive for male but not female Wistar rats in the DWT. Whether this is due to sex differences in light sensitivity or if females respond with a different behavioural strategy in response to bright light, which could not be detected in the DWT, remains to be elucidated.

Origin of the Relative Afferent Pupillary Defect in Optic Tract Lesions

To determine the percent decussation of pupil input fibers in humans and to explain the size and range of the log unit relative afferent pupillary defect (RAPD) in patients with optic tract lesions. Experimental study. Five patients with a unilateral optic tract lesion. The pupil response from light stimulation of the nasal hemifield, temporal hemifield, and full field of each eye of 5 patients with a unilateral optic tract lesion was recorded using computerized binocular infrared pupillography. Six stimulus light intensities, separated by 0.5-log unit steps, were used; 12 stimulus repetitions were given for each stimulus condition. For each stimulus condition, the pupil response of each eye was characterized by plotting the mean pupil contraction amplitude as a function of stimulus light intensity. The percentage of decussating afferent pupillomotor input fibers was calculated from the ratio of the maximal pupil contractions elicited from each eye. The RAPD was determined pupillographically from full-field stimulation to each eye. In all patients, the pupil response from the functioning temporal hemifield ipsilateral to the tract lesion was greater than that from the functioning contralateral nasal hemifield. This temporal-nasal asymmetry increased with increasing stimulus intensity and was similar in hemifield and full-field stimuli, eventually saturating at maximal light intensity. The log unit RAPD did not correlate with the estimated percentage of decussating pupil fibers, which ranged from 54% to 67%. In patients with a unilateral optic tract lesion, the pupillary responses from full-field stimulation to each eye are the same as comparing the functioning temporal field with the functioning nasal field. The percentage of decussating fibers is reflected in the ratio of the maximal pupil contraction amplitudes resulting from stimulus input between the two eyes. The RAPD that occurs in this setting reflects the difference in light sensitivity between the intact temporal and nasal hemifields. Its magnitude does not correlate with the difference in the number of crossed and uncrossed axons, but its sidedness contralateral to the side of the optic tract lesion is consistent with the greater percentage of decussating pupillomotor input.

The effect of gender on the melatonin suppression by light: a dose response relationship.

It is well known that light is an inhibitor of pineal melatonin secretion in humans. However, the effect of gender on the melatonin suppression by dim and bright light is still controversial. The present study investigated the effect of gender on the suppression of melatonin at five light intensities (0, 200, 500, 1,000, 3,000 lux). Five healthy men and women attended five testing sessions separated by one week. At each session, subjects were exposed to light from midnight to 0100 hours in a sitting position. Blood samples where collected at regular intervals and plasma melatonin concentration was measured using a specific radioimmunoassay. No gender differences were found in melatonin suppression by light at any of the five light intensities (p > 0.1). Furthermore, the mean melatonin suppression by light in both males and females was dose dependent (17% [200 lux], 40% [500 lux], 56% [1,000 lux] and 74% [3,000 lux]). Our findings suggest that melatonin suppression by light in intensity dependent, with no gender differences in light sensitivity.

Light sensitivity in larval fishes: Implications for vertical zonation in the pelagic zone

Larval fishes exhibit marked vertical zonation patterns that are important in planktonic predator‐prey interactions. This zonation has been related to both proximate physical (e.g., light intensity) and ultimate biological factors (e.g., predator risk, prey availability). We hypothesize that changes in visual sensitivity and feeding performance in larval fishes provide a constraint on depth distributions and that this constraint may represent the major determinant of vertical distribution patterns. To test the generality of the relationship between larval age and visual sensitivity, larvae were obtained from captive breeding adults of seven species (three Apogonidae and four Pomacentridae). The lowest light intensity at which feeding behavior occurred was measured using infrared video techniques with natural prey items. The visual sensitivity of the larvae, measured as initiation of feeding, increased by about 3 orders‐of‐magnitude during the larval phase. The abilities of the larvae were broadly similar within families, but there were marked differences between families. Pomacentrids were about an order‐of‐magnitude less light‐sensitive than apogonids. Larval apogonids are potentially capable of feeding at a depth of about 100 m in clear tropical waters at 4 mm standard length (SL) and to 200 m at 12 mm SL. The patterns of ontogenetic and phylogenetic differences in light sensitivity are consistent with field observations on the vertical distributions of larvae in these taxa.

Light-Induced Discomfort and Pain in Migraine

Quantitative thresholds for discomfort and pain with monocular and binocular light stimuli were measured in 67 controls and 67 migraine patients (37 migraine with aura and 30 migraine without aura). Patients were more photophobic during attack than outside attack (p < 0.03), and they were more sensitive to light than controls even between attacks (p < or = 0.0001). We found no differences in light sensitivity between migraine with aura and migraine without aura (p > or = 0.93). Unilateral pain affected light sensitivity on both sides. When asked with a questionnaire, 74% of patients answered that they were sensitive to light outside attack and 100% were sensitive during attack. Pain thresholds were generally lower among sensitive than non-sensitive patients (p = 0.004), indicating some agreement between subjective opinion and objective measurements of photophobia. Photophobia seems to be an intrinsic property of migraineurs. It is increased by migraine pain, but seems to be unrelated to migraine characteristics such as nausea, severity of attacks, pain character and pain laterality.

REACTION NORMS OF MORPHOLOGICAL AND LIFE-HISTORY TRAITS TO LIGHT AVAILABILITY IN IMPATIENS CAPENSIS.

For plants, light availability is an important environmental factor that varies both within and between populations. Although the existence of sun and shade "ecotypes" is controversial, it is often assumed that trade-offs may exist between performance in sun and in shade. This study therefore investigated variation in reaction norms to light availability within and between two neighboring natural populations of the annual Impatiens capensis, one in full sun and the other in a forest understory. Seedlings were collected randomly from both populations and grown to maturity in a greenhouse under two light conditions: full light and 18% of full light. Selfed full-sib seed families were collected from plants from both populations grown in both parental light environments. To characterize family reaction norms, seedlings from each family were divided into the same two light treatments and individuals were scored for a variety of morphological and life-history traits. The maternal light environment had little impact on progeny reaction norms. However, the two study populations differed both qualitatively and quantitatively in plastic response to light availability (indicated by significant population x environment interactions in mixed-model ANCOVA). Much of this difference was attributable to population differences in light sensitivity of axillary meristem allocation patterns, which produced concurrent differences in reaction norms for a suite of developmentally linked traits. Within each population, different sets of traits displayed significant variation in plasticity (indicated by significant family x environment interactions). Thus, the genetic potential for evolutionary response to selection in heterogeneous light environments may differ dramatically between neighboring plant populations. Between-environment genetic correlations were largely positive in the woods population and positive or nonsignificant in the sun population; there was no evidence for performance trade-offs across environments or sun or shade "specialist" genotypes within either population. There was little evidence that population differences represented adaptive differentiation for sun or shade; rather, the results suggested the hypothesis of differential selection on patterns of meristem allocation caused by population differences in timing of mortality and intensity of competition.