Spectral dependency of the human pupillary light reflex. Influences of pre-adaptation and chronotype

Non-visual photoreceptors (ipRGCs) and rods both exert a strong influence on the human pupil, yet pupil models regularly use cone-derived sensitivity as their basis. This inconsistency is further exacerbated by the fact that circadian effects can modulate the wavelength sensitivity. We assessed the pupillary reaction to narrowband light stimuli in the mesopic range. Pupil size for eighty-three healthy participants with normal color vision was measured in nine experimental protocols with varying series of continuous or discontinuous light stimuli under Ganzfeld conditions, presented after 90 seconds of dark adaptation. One hundred and fifty series of stimulation were conducted across three experiments, and were analyzed for wavelength-dependency on the normalized pupillary constriction (nPC), conditional on experimental settings and individual traits. Traits were surveyed by questionnaire; color vision was tested by Ishihara plates or the Lanthony D15 test. Data were analyzed with generalized additive mixed models (GAMM). The normalized pupillary constriction response is consistent with L+M-cone derived sensitivity when the series of light stimuli is continuous, i.e., is not interrupted by periods of darkness, but not otherwise. The results also show that a mesopic illuminance weighing led to an overall best prediction of pupillary constriction compared to other types of illuminance measures. IpRGC influence on nPC is not readily apparent from the results. When we explored the interaction of chronotype and time of day on the wavelength dependency, differences consistent with ipRGC influence became apparent. The models indicate that subjects of differing chronotype show a heightened or lowered sensitivity to short wavelengths, depending on their time of preference. IpRGC influence is also seen in the post-illumination pupil reflex if the prior light-stimulus duration is one second. However, shorter wavelengths than expected become more important if the light-stimulus duration is fifteen or thirty seconds. The influence of sex on nPC was present, but showed no interaction with wavelength. Our results help to define the conditions, under which the different wavelength sensitivities in the literature hold up for narrowband light settings. The chronotype effect might signify a mechanism for strengthening the individual´s chronotype. It could also be the result of the participant’s prior exposure to light (light history). Our explorative findings for this effect demand replication in a controlled study.

Memory and habituation to harmful and non-harmful stimuli in a field population of the sensitive plant, Mimosa pudica

Mimosa pudica is a Neotropical legume that closes its leaves rapidly in response to touch stimulation, hypothetically as herbivory defence. Habituation to non-harmful stimuli and long-term memory of past events have been demonstrated in this species, the former with relatively heavy objects and the latter under laboratory conditions. This species should not habituate to harmful stimuli if leaf movement is a response to herbivore damage. We tested in Monteverde, Costa Rica, whether (1) memory occurs in wild plants, (2) whether habituation occurs under harmful stimuli: simulated herbivory, and (3) whether wild plants can habituate to light non-harmful stimuli. The degree of closing of the leaflets and time until reopening was measured in response to repeated harmful and non-harmful stimuli. The results showed habituation to repeated non-harmful very light stimuli and showed lack of habituation to simulated leaf damage. Wild plants also showed faster rehabituation to repeated non-harmful stimuli when they had been exposed 15 days previously, suggesting possible long-term memory. These results indicate that wild plants are capable of (1) distinguishing between harmful and non-harmful stimuli (only habituating to the latter), (2) memorizing previous events, and 3) habituating very light tactile stimuli commonly experienced in the field.

Handheld chromatic pupillometry can accurately and rapidly reveal functional loss in glaucoma

Background/aimsEarly detection and treatment of glaucoma can delay vision loss. In this study, we evaluate the performance of handheld chromatic pupillometry (HCP) for the objective and rapid detection of functional loss in glaucoma.MethodsIn this clinic-based, prospective study, we enrolled 149 patients (median (IQR) years: 68.5 (13.6) years) with confirmed glaucoma and 173 healthy controls (55.2 (26.7) years). Changes in pupil size in response to 9 s of exponentially increasing blue (469 nm) and red (640 nm) light-stimuli were assessed monocularly using a custom-built handheld pupillometer. Pupillometric features were extracted from individual traces and compared between groups. Features with the highest classification potential, selected using a gradient boosting machine technique, were incorporated into a generalised linear model for glaucoma classification. Receiver operating characteristic curve analyses (ROC) were used to compare the performance of HCP, optical coherence tomography (OCT) and Humphrey Visual Field (HVF).ResultsPupillary light responses were altered in glaucoma compared with controls. For glaucoma classification, HCP yielded an area under the ROC curve (AUC) of 0.94 (95% CI 0.91 to 0.96), a sensitivity of 87.9% and specificity of 88.4%. The classification performance of HCP in early-moderate glaucoma (visual field mean deviation (VFMD) > -12 dB; AUC=0.91 (95% CI 0.87 to 0.95)) was similar to HVF (AUC=0.91) and reduced compared with OCT (AUC=0.97; p=0.01). For severe glaucoma (VFMD ≤ -12 dB), HCP had an excellent classification performance (AUC=0.98, 95% CI 0.97 to 1) that was similar to HVF and OCT.ConclusionHCP allows for an accurate, objective and rapid detection of functional loss in glaucomatous eyes of different severities.

Comprehensive Management of Congenital Cataract in Dizygotic Twin Babies

Introduction: One of the leading causes of infant blindness is cataract. The prevalence of congenital cataract has been estimated in the range between 1 and 15 per 10.000 children globally. Congenital cataract in twin babies is a rare case. This case will report the outcome of comprehensive management of congenital cataract in dizygotic twin babies. Case presentation: Eight months old dizygotic twin babies came to our clinic with the primary complaint of whitish appearance in the pupil of both eyes since birth. They were born aterm with cesarean delivery. The birth weight was 2.700 g and 3.100 g respectively. They were the fourth and fifth children in the family. There was no family history of congenital cataract. The visual acuity of both eyes was positive response to light stimuli. The cataract was bilateral and dense on both babies. Fundus reflex and TORCH examinations were negative. Ultrasonography (USG) of the retina was normal on both babies. Conclusions: Isolated congenital cataract in twin babies is an unusual condition that should be treated comprehensively. Congenital cataract may cause deprivation amblyopia, refractive amblyopia, and permanent vision impairment. Early diagnosis and quick treatment, such as surgical timing and visual rehabilitation, are critical to perform successful management. Comprehensive care is required to monitor the visual result of cataract surgery.

Transient inhibition to light explains stronger V1 responses to dark stimuli

Neurons in the primary visual cortex (V1) receive excitation and inhibition from two different pathways processing lightness (ON) and darkness (OFF). V1 neurons overall respond more strongly to dark than light stimuli (Yeh, Xing and Shapley, 2010; Kremkow et al., 2014), consistent with a preponderance of darker regions in natural images (Ratliff et al., 2010), as well as human psychophysics (Buchner & Baumgartner, 2007). However, it has been unclear whether this "dark-dominance" is due to more excitation from the OFF pathway (Jin et al., 2008) or more inhibition from the ON pathway (Taylor et al., 2018). To understand the mechanisms behind dark-dominance, we record electrophysiological responses of individual simple-type V1 neurons to natural image stimuli and then train biologically inspired convolutional neural networks to predict the neuronal responses. Analyzing a sample of 74 neurons (in anesthetized, paralyzed cats) has revealed their responses to be more driven by dark than light stimuli, consistent with previous investigations (Yeh et al., 2010; Kremkow et al., 2013). We show this asymmetry to be predominantly due to slower inhibition to dark stimuli rather than by stronger excitation from the thalamocortical OFF pathway. Consistent with dark-dominant neurons having faster responses than light-dominant neurons (Komban et al., 2014), we find dark-dominance to solely occur in the early latencies of neuronal responses. Neurons that are strongly dark-dominated also tend to be less orientation selective. This novel approach gives us new insight into the dark-dominance phenomenon and provides an avenue to address new questions about excitatory and inhibitory integration in cortical neurons.

Light-stimulus intensity modulates startle reflex habituation in larval zebrafish

The startle reflex in larval zebrafish describes a C-bend of the body occurring in response to sudden, unexpected, stimuli of different sensory modalities. Alterations in the startle reflex habituation (SRH) have been reported in various human and animal models of neurological and psychiatric conditions and are hence considered an important behavioural marker of neurophysiological function. The amplitude, offset and decay constant of the auditory SRH in larval zebrafish have recently been characterised, revealing that the measures are affected by variation in vibratory frequency, intensity, and interstimulus-interval. Currently, no study provides a model-based analysis of the effect of physical properties of light stimuli on the visual SRH. This study assessed the effect of incremental light-stimulus intensity on the SRH of larval zebrafish through a repeated-measures design. Their total locomotor responses were normalised for the time factor, based on the behaviour of a (non-stimulated) control group. A linear regression indicated that light intensity positively predicts locomotor responses due to larger SRH decay constants and offsets. The conclusions of this study provide important insights as to the effect of light properties on the SRH in larval zebrafish. Our methodology and findings constitute a relevant reference framework for further investigation in translational neurophysiological research.

Bioluminescence and Photoreception in Unicellular Organisms: Light-Signalling in a Bio-Communication Perspective

Bioluminescence, the emission of light catalysed by luciferases, has evolved in many taxa from bacteria to vertebrates and is predominant in the marine environment. It is now well established that in animals possessing a nervous system capable of integrating light stimuli, bioluminescence triggers various behavioural responses and plays a role in intra- or interspecific visual communication. The function of light emission in unicellular organisms is less clear and it is currently thought that it has evolved in an ecological framework, to be perceived by visual animals. For example, while it is thought that bioluminescence allows bacteria to be ingested by zooplankton or fish, providing them with favourable conditions for growth and dispersal, the luminous flashes emitted by dinoflagellates may have evolved as an anti-predation system against copepods. In this short review, we re-examine this paradigm in light of recent findings in microorganism photoreception, signal integration and complex behaviours. Numerous studies show that on the one hand, bacteria and protists, whether autotrophs or heterotrophs, possess a variety of photoreceptors capable of perceiving and integrating light stimuli of different wavelengths. Single-cell light-perception produces responses ranging from phototaxis to more complex behaviours. On the other hand, there is growing evidence that unicellular prokaryotes and eukaryotes can perform complex tasks ranging from habituation and decision-making to associative learning, despite lacking a nervous system. Here, we focus our analysis on two taxa, bacteria and dinoflagellates, whose bioluminescence is well studied. We propose the hypothesis that similar to visual animals, the interplay between light-emission and reception could play multiple roles in intra- and interspecific communication and participate in complex behaviour in the unicellular world.

Disturbed retinoid metabolism upon loss of rlbp1a impairs cone function and leads to subretinal lipid deposits and photoreceptor degeneration in the zebrafish retina

The RLBP1 gene encodes the 36 kDa cellular retinaldehyde binding protein, CRALBP, a soluble retinoid carrier, in the visual cycle of the eyes. Mutations in RLBP1 are associated with recessively inherited clinical phenotypes, including Bothnia dystrophy, retinitis pigmentosa, retinitis punctata albescens, fundus albipunctatus, and Newfoundland rod-cone dystrophy. However, the etiology of these retinal disorders is not well understood. Here, we generated homologous zebrafish models to bridge this knowledge gap. Duplication of the rlbp1 gene in zebrafish and cell-specific expression of the paralogs rlbp1a in the retinal pigment epithelium and rlbp1b in Müller glial cells allowed us to create intrinsically cell type-specific knockout fish lines. Using rlbp1a and rlbp1b single and double mutants, we investigated the pathological effects on visual function. Our analyses revealed that rlbp1a was essential for cone photoreceptor function and chromophore metabolism in the fish eyes. rlbp1a mutant fish displayed reduced chromophore levels and attenuated cone photoreceptor responses to light stimuli. They accumulated 11-cis and all-trans-retinyl esters which displayed as enlarged lipid droplets in the RPE reminiscent of the subretinal yellow-white lesions in patients with RLBP1 mutations. During aging, these fish developed retinal thinning and cone and rod photoreceptor dystrophy. In contrast, rlbp1b mutants did not display impaired vision. The double mutant essentially replicated the phenotype of the rlbp1a single mutant. Together, our study showed that the rlbp1a zebrafish mutant recapitulated many features of human blinding diseases caused by RLBP1 mutations and provided novel insights into the pathways for chromophore regeneration of cone photoreceptors.