Vision: A specialized pathway for pigment regeneration in cones.

Vision relies on two types of photoreceptor cells, rods and cones. Rods outnumber cones in the retinas of humans and most other vertebrate species, yet the contribution of cones to our vision is far more impactful than rods. A new study reveals an elegant enzymatic mechanism that favors light perception by cones under daylight conditions when rods are saturated by light and contribute little to useful vision.

Utility index and vision-related quality of life in patients awaiting specialist eye care.

OBJECTIVES: This study aimed to ascertain utility and vision-related quality of life in patients awaiting access to specialist eye care. A secondary aim was to evaluate the association of utility indices with demographic profile and waiting time. METHODS: Consecutive patients that had been waiting for ophthalmology care answered the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25). The questionnaire was administered when patients arrived at the clinics for their first visit. We derived a utility index (VFQ-UI) from the patients' responses, then calculated the correlation between this index and waiting time and compared utility across demographic subgroups stratified by age, sex, and care setting. RESULTS: 536 individuals participated in the study (mean age 52.9±16.6 years; 370 women, 69% women). The median utility index was 0.85 (interquartile range [IQR] 0.70-0.92; minimum 0.40, maximum 0.97). The mean VFQ-25 score was 70.88±14.59. Utility correlated weakly and nonsignificantly with waiting time (-0.05, P = 0.24). It did not vary across age groups (P = 0.85) or care settings (P = 0.77). Utility was significantly lower for women (0.84, IQR 0.70-0.92) than men (0.87, IQR 0.73-0.93, P = 0.03), but the magnitude of this difference was small (Cohen's d = 0.13). CONCLUSION: Patients awaiting access to ophthalmology care had a utility index of 0.85 on a scale of 0 to 1. This measurement was not previously reported in the literature. Utility measures can provide insight into patients' perspectives and support economic health analyses and inform health policies.

Modulating amacrine cell-derived dopamine signaling promotes optic nerve regeneration and preserves visual function.

As part of the central nervous system, the optic nerve, composed of axons from retinal ganglion cells (RGCs), generally fails to regenerate on its own when injured in adult mammals. An innovative approach to promoting optic nerve regeneration involves manipulating the interactions between amacrine cells (ACs) and RGCs. Here, we identified a unique AC subtype, dopaminergic ACs (DACs), that responded early after optic nerve crush by down-regulating neuronal activity and reducing retinal dopamine (DA) release. Activating DACs or augmenting DA release with levodopa demonstrated neuroprotective effects and modestly enhanced axon regeneration. Within this context, we pinpointed the DA receptor D1 (DRD1) as a critical mediator of DAC-derived DA and showed that RGC-specific Drd1 overexpression effectively overcame subtype-specific barriers to regeneration. This strategy markedly boosted RGC survival and axon regeneration after crush and preserved vision in a glaucoma model. This study unveils the crucial role of DAC-derived DA signaling in optic nerve regeneration, holding promise for therapeutic insights into neural repair.

Practical Advice on Measuring and Applying Light for Laboratory Mammals.

Light is recognized as an important component of the environment for laboratory animals. It supports vision, sets the phase of circadian clocks, and drives wide-ranging adjustments in physiological and behavioral state. Manipulating light is meanwhile a key experimental approach in the fields of vision science and chronobiology. Nevertheless, until recently, there has been no consensus on methods for quantifying light as experienced by laboratory animals. Widely adopted practices employ metrics such as illuminance (units = lux) that are designed to quantify light as experienced by human observers. These weight energy across the spectrum according to a spectral sensitivity profile for human vision that is not widely replicated for non-human species. Recently, a Consensus View was published that proposes methods of light measurement and standardization that take account of these species-specific differences in wavelength sensitivity. Here, we draw upon the contents of that consensus to provide simplified advice on light measurement in laboratory mammal experimentation and husbandry and quantitative guidance on what constitutes appropriate lighting for both visual and circadian function.

The First Steps of the Visual Cycle in Human Rod and Cone Photoreceptors.

Purpose: Light detection destroys the visual pigment. Its regeneration, necessary for the recovery of light sensitivity, is accomplished through the visual cycle. Release of all-trans retinal by the light-activated visual pigment and its reduction to all-trans retinol comprise the first steps of the visual cycle. In this study, we determined the kinetics of all-trans retinol formation in human rod and cone photoreceptors. Methods: Single living rod and cone photoreceptors were isolated from the retinas of human cadaver eyes (ages 21 to 90 years). Formation of all-trans retinol was measured by imaging its outer segment fluorescence (excitation, 360 nm; emission, >420 nm). The extent of conversion of released all-trans retinal to all-trans retinol was determined by measuring the fluorescence excited by 340 and 380 nm. Measurements were repeated with photoreceptors isolated from Macaca fascicularis retinas. Experiments were carried out at 37°C. Results: We found that ∼80% to 90% of all-trans retinal released by the light-activated pigment is converted to all-trans retinol, with a rate constant of 0.24 to 0.55 min-1 in human rods and ∼1.8 min-1 in human cones. In M. fascicularis rods and cones, the rate constants were 0.38 ± 0.08 min-1 and 4.0 ± 1.1 min-1, respectively. These kinetics are several times faster than those measured in other vertebrates. Interphotoreceptor retinoid-binding protein facilitated the removal of all-trans retinol from human rods. Conclusions: The first steps of the visual cycle in human photoreceptors are several times faster than in other vertebrates and in line with the rapid recovery of light sensitivity exhibited by the human visual system.

Effect of juggling expertise on pointing performance in peripheral vision.

Juggling is a very complex activity requiring motor, visual and coordination skills. Expert jugglers experience a "third eye" monitoring leftward and rightward ball zenith positions alternately, in the upper visual fields, while maintaining their gaze straight-ahead. This "third eye" reduces their motor noise (improved body stability and decrease in hand movement variability) as it avoids the numerous head and eye movements that add noise into the system and make trajectories more uncertain. Neuroimaging studies have shown that learning to juggle induces white and grey matter hypertrophy at the posterior intraparietal sulcus. Damage to this brain region leads to optic ataxia, a clinical condition characterised by peripheral pointing bias toward gaze position. We predicted that expert jugglers would, conversely, present better accuracy in a peripheral pointing task. The mean pointing accuracy of expert jugglers was better for peripheral pointing within the upper visual field, compatible with their subjective experience of the "third eye". Further analyses showed that experts exhibited much less between-subject variability than beginners, reinforcing the interpretation of a vertically asymmetrical calibration of peripheral space, characteristic of juggling and homogenous in the expert group. On the contrary, individual pointing variability did not differ between groups neither globally nor in any sector of space, showing that the reduced motor noise of experts in juggling did not transfer to pointing. It is concluded that the plasticity of the posterior intraparietal sulcus related to juggling expertise does not consist of globally improved visual-to-motor ability. It rather consists of peripheral space calibration by practicing horizontal covert shifts of the attentional spotlight within the upper visual field, between left and right ball zenith positions.

Structurally-constrained encoding framework using a multi-voxel reduced-rank latent model for human natural vision.

Objective. Voxel-wise visual encoding models based on convolutional neural networks (CNNs) have emerged as one of the prominent predictive tools of human brain activity via functional magnetic resonance imaging signals. While CNN-based models imitate the hierarchical structure of the human visual cortex to generate explainable features in response to natural visual stimuli, there is still a need for a brain-inspired model to predict brain responses accurately based on biomedical data.Approach. To bridge this gap, we propose a response prediction module called the Structurally Constrained Multi-Output (SCMO) module to include homologous correlations that arise between a group of voxels in a cortical region and predict more accurate responses.Main results. This module employs all the responses across a visual area to predict individual voxel-wise BOLD responses and therefore accounts for the population activity and collective behavior of voxels. Such a module can determine the relationships within each visual region by creating a structure matrix that represents the underlying voxel-to-voxel interactions. Moreover, since each response module in visual encoding tasks relies on the image features, we conducted experiments using two different feature extraction modules to assess the predictive performance of our proposed module. Specifically, we employed a recurrent CNN that integrates both feedforward and recurrent interactions, as well as the popular AlexNet model that utilizes feedforward connections.Significance.We demonstrate that the proposed framework provides a reliable predictive ability to generate brain responses across multiple areas, outperforming benchmark models in terms of stability and coherency of features.

Light Sensing beyond Vision: Focusing on a Possible Role for the FICZ/AhR Complex in Skin Optotransduction.

Although our skin is not the primary visual organ in humans, it acts as a light sensor, playing a significant role in maintaining our health and overall well-being. Thanks to the presence of a complex and sophisticated optotransduction system, the skin interacts with the visible part of the electromagnetic spectrum and with ultraviolet (UV) radiation. Following a brief overview describing the main photosensitive molecules that detect specific electromagnetic radiation and their associated cell pathways, we analyze their impact on physiological functions such as melanogenesis, immune response, circadian rhythms, and mood regulation. In this paper, we focus on 6-formylindolo[3,2-b]carbazole (FICZ), a photo oxidation derivative of the essential amino acid tryptophan (Trp). This molecule is the best endogenous agonist of the Aryl hydrocarbon Receptor (AhR), an evolutionarily conserved transcription factor, traditionally recognized as a signal transducer of both exogenous and endogenous chemical signals. Increasing evidence indicates that AhR is also involved in light sensing within the skin, primarily due to its ligand FICZ, which acts as both a chromophore and a photosensitizer. The biochemical reactions triggered by their interaction impact diverse functions and convey crucial data to our body, thus adding a piece to the complex puzzle of pathways that allow us to decode and elaborate environmental stimuli.

Moving from stable standing to single-limb stance or an up-on-the-toes position: The importance of vision to dynamic balance control.

Understanding the contribution vision has to dynamic balance control may help in understanding where/why loss of balance occurs during everyday locomotion. The current study determined how body-centre-of-mass (BCoM) dynamics and postural stability when moving to and holding a single-limb-stance (SS) or an up-on-the-toes (UTT) position were affected by visual occlusion. From standing on a force platform, 18 adults (mean (SD) 26.7 (4.8) years; 1.73 (0.08) m; 84.0 (22.9) kg; 7 females) completed repeated trials (x3) with and without vision in which they moved to either a SS or an UTT position (order countered-balanced), and attempted to hold that position for 2 (SS) or 5 (UTT) seconds before returning to standing. UTT trials were also repeated at a fast speed, and SS trials were repeated using both the dominant and non-dominant limb. BCoM dynamics were assessed by analysing the displacement and peak velocity of the centre-of-pressure (CoP) when moving to and from the SS and UTT positions. Balance stability was the variability in the CoP displacement/velocity when holding these positions. Results indicate that under visual occlusion, the peak CoP velocity when moving to the SS or UTT position was reduced (ES, 0.67 and 0.68, respectively), suggesting greater caution. Both the variability in the CoP displacement/velocity when holding these positions and the peak CoP velocity when returning to flat-standing increased (SS: ES, 1.0 and 0.86, respectively; UTT: ES 1.26 and 0.66, respectively), suggesting, respectively, greater instability and poorer control. The poorer control in SS trials, occurred when returning to standing from the SS position held on the non-dominant limb, and correspondingly, the reduction in SS duration when vision was occluded was greater for the non-dominant limb trails (limb-vision interaction; p = 0.042). This suggests that movements initiated/controlled by the non-dominant limb are more reliant on visual feedback than those initiated/controlled by the dominant limb.

Multimodal interactions in Stomoxys navigation reveal synergy between olfaction and vision.

Stomoxys flies exhibit an attraction toward objects that offer no rewards, such as traps and targets devoid of blood or nectar incentives. This behavior provides an opportunity to develop effective tools for vector control and monitoring. However, for these systems to be sustainable and eco-friendly, the visual cues used must be specific to target vector(s). In this study, we modified the existing blue Vavoua trap, which was originally designed to attract biting flies, to create a deceptive host attraction system specifically biased toward attracting Stomoxys. Our research revealed that Stomoxys flies are attracted to various colors, with red proving to be the most attractive and selective color for Stomoxys compared to the other colors tested. Interestingly, our investigation of the cattle-Stomoxys interaction demonstrated that Stomoxys flies do not prefer a specific livestock fur color phenotype, despite variation in the spectrum. To create a realistic sensory impression of the trap in the Stomoxys nervous system, we incorporated olfactory cues from livestock host odors that significantly increased trap catches. The optimized novel polymer bead dispenser is capable of effectively releasing the attractive odor carvone + p-cresol, with strong plume strands and longevity. Overall, red trap baited with polymer bead dispenser is environmentally preferred.

Evolution: Decoding the adaptation of multi-eyed visual systems.

Many invertebrates possess more than two pairs of eyes - but does eye redundancy aid in ecological diversification? A new study finds varied size adaptation of different eye pairs in spiders, demonstrating how developmental modularity of multi-eyed systems effectively balances selective pressures.

Short communication: Maintained visual performance in birds under high altitude hypoxia.

Birds are highly dependent on their vision for orientation and navigation. The avian eye differs from the mammalian eye as the retina is avascular, leaving the inner, highly metabolically active layers with a very long diffusion distance to the oxygen supply. During flight at high altitudes, birds face a decrease in environmental oxygen partial pressure, which leads to a decrease in arterial oxygen levels. Since oxygen perfusion to the retina is already limited in birds, we hypothesize that visual function is impaired by low oxygen availability. However, the visual performance of birds exposed to hypoxia has not been evaluated before. Here, we assess the optomotor response (OMR) in zebra finches under simulated high-altitude hypoxia (10%) and show that the OMR is largely maintained under hypoxia with only a modest reduction in OMR, demonstrating that birds can largely maintain visual function at high altitudes. The method of our study does not provide insight into the mechanisms involved, but our findings suggest that birds have evolved physiological mechanisms for retinal function at low tissue oxygen levels.

Tadpoles rely on mechanosensory stimuli for communication when visual capabilities are poor.

The ways in which animals sense the world changes throughout development. For example, young of many species have limited visual capabilities, but still make social decisions, likely based on information gathered through other sensory modalities. Poison frog tadpoles display complex social behaviors that have been suggested to rely on vision despite a century of research indicating tadpoles have poorly-developed visual systems relative to adults. Alternatively, other sensory modalities, such as the lateral line system, are functional at hatching in frogs and may guide social decisions while other sensory systems mature. Here, we examined development of the mechanosensory lateral line and visual systems in tadpoles of the mimic poison frog (Ranitomeya imitator) that use vibrational begging displays to stimulate egg feeding from their mothers. We found that tadpoles hatch with a fully developed lateral line system. While begging behavior increases with development, ablating the lateral line system inhibited begging in pre-metamorphic tadpoles, but not in metamorphic tadpoles. We also found that the increase in begging and decrease in reliance on the lateral line co-occurs with increased retinal neural activity and gene expression associated with eye development. Using the neural tracer neurobiotin, we found that axonal innervations from the eye to the brain proliferate during metamorphosis, with few retinotectal connections in recently-hatched tadpoles. We then tested visual function in a phototaxis assay and found tadpoles prefer darker environments. The strength of this preference increased with developmental stage, but eyes were not required for this behavior, possibly indicating a role for the pineal gland. Together, these data suggest that tadpoles rely on different sensory modalities for social interactions across development and that the development of sensory systems in socially complex poison frog tadpoles is similar to that of other frog species.

Alpha and theta rhythm support perceptual and attentional sampling in vision.

The visual system operates rhythmically, through timely coordinated perceptual and attentional processes, involving coexisting patterns in the alpha range (7-13 Hz) at ∼10 Hz, and theta (3-6 Hz) range, respectively. Here we aimed to disambiguate whether variations in task requirements, in terms of attentional demand and side of target presentation, might influence the occurrence of either perceptual or attentional components in behavioral visual performance, also uncovering possible differences in the sampling mechanisms of the two cerebral hemispheres. To this aim, visuospatial performance was densely sampled in two versions of a visual detection task where the side of target presentation was fixed (Task 1), with participants monitoring one single hemifield, or randomly varying across trials, with participants monitoring both hemifields simultaneously (Task 2). Performance was analyzed through spectral decomposition, to reveal behavioral oscillatory patterns. For Task 1, when attentional resources where focused on one hemifield only, the results revealed an oscillatory pattern fluctuating at ∼10 Hz and ∼6-9 Hz, for stimuli presented to the left and the right hemifield, respectively, possibly representing a perceptual sampling mechanism with different efficiency within the left and the right hemispheres. For Task 2, when attentional resources were simultaneously deployed to the two hemifields, a ∼5 Hz rhythm emerged both for stimuli presented to the left and the right, reflecting an attentional sampling process, equally supported by the two hemispheres. Overall, the results suggest that distinct perceptual and attentional sampling mechanisms operate at different oscillatory frequencies and their prevalence and hemispheric lateralization depends on task requirements.

Characterizing medaka visual features using a high-throughput optomotor response assay.

Medaka fish (Oryzias latipes) is a powerful model to study genetics underlying the developmental and functional traits of the vertebrate visual system. We established a simple and high-throughput optomotor response (OMR) assay utilizing medaka larvae to study visual functions including visual acuity and contrast sensitivity. Our assay presents multiple adjustable stripes in motion to individual fish in a linear arena. For that the OMR assay employs a tablet display and the Fish Stripes software to adjust speed, width, color, and contrast of the stripes. Our results demonstrated that optomotor responses were robustly induced by black and white stripes presented from below in the linear-pool-arena. We detected robust strain specific differences in the OMR when comparing long established medaka inbred strains. We observed an interesting training effect upon the initial exposure of larvae to thick stripes, which allowed them to better respond to narrower stripes. The OMR setup and protocol presented here provide an efficient tool for quantitative phenotype mapping, addressing visual acuity, trainability of cortical neurons, color sensitivity, locomotor response, retinal regeneration and others. Our open-source setup presented here provides a crucial prerequisite for ultimately addressing the genetic basis of those processes.

Biomarker evidence of early vision and rod energy-linked pathophysiology benefits from very low dose DMSO in 5xFAD mice.

Here, we test whether early visual and OCT rod energy-linked biomarkers indicating pathophysiology in nicotinamide nucleotide transhydrogenase (Nnt)-null 5xFAD mice also occur in Nnt-intact 5xFAD mice and whether these biomarkers can be pharmacologically treated. Four-month-old wild-type or 5xFAD C57BL/6 substrains with either a null (B6J) Nnt or intact Nnt gene (B6NTac) and 5xFAD B6J mice treated for one month with either R-carvedilol + vehicle or only vehicle (0.01% DMSO) were studied. The contrast sensitivity (CS), external limiting membrane-retinal pigment epithelium (ELM-RPE) thickness (a proxy for low pH-triggered water removal), profile shape of the hyperreflective band just posterior to the ELM (i.e., the mitochondrial configuration within photoreceptors per aspect ratio [MCP/AR]), and retinal laminar thickness were measured. Both wild-type substrains showed similar visual performance indices and dark-evoked ELM-RPE contraction. The lack of a light-dark change in B6NTac MCP/AR, unlike in B6J mice, is consistent with relatively greater mitochondrial efficiency. 5xFAD B6J mice, but not 5xFAD B6NTac mice, showed lower-than-WT CS. Light-adapted 5xFAD substrains both showed abnormal ELM-RPE contraction and greater-than-WT MCP/AR contraction. The inner retina and superior outer retina were thinner. Treating 5xFAD B6J mice with R-carvedilol + DMSO or DMSO alone corrected CS and ELM-RPE contraction but not supernormal MCP/AR contraction or laminar thinning. These results provide biomarker evidence for prodromal photoreceptor mitochondrial dysfunction/oxidative stress/oxidative damage, which is unrelated to visual performance, as well as the presence of the Nnt gene. This pathophysiology is druggable in 5xFAD mice.

Noninvasive imaging-guided ultrasonic neurostimulation with arbitrary 2D patterns and its application for high-quality vision restoration.

Retinal degeneration, a leading cause of irreversible low vision and blindness globally, can be partially addressed by retina prostheses which stimulate remaining neurons in the retina. However, existing electrode-based treatments are invasive, posing substantial risks to patients and healthcare providers. Here, we introduce a completely noninvasive ultrasonic retina prosthesis, featuring a customized ultrasound two-dimensional array which allows for simultaneous imaging and stimulation. With synchronous three-dimensional imaging guidance and auto-alignment technology, ultrasonic retina prosthesis can generate programmed ultrasound waves to dynamically and precisely form arbitrary wave patterns on the retina. Neuron responses in the brain's visual center mirrored these patterns, evidencing successful artificial vision creation, which was further corroborated in behavior experiments. Quantitative analysis of the spatial-temporal resolution and field of view demonstrated advanced performance of ultrasonic retina prosthesis and elucidated the biophysical mechanism of retinal stimulation. As a noninvasive blindness prosthesis, ultrasonic retina prosthesis could lead to a more effective, widely acceptable treatment for blind patients. Its real-time imaging-guided stimulation strategy with a single ultrasound array, could also benefit ultrasound neurostimulation in other diseases.

Primacy of vision shapes behavioral strategies and neural substrates of spatial navigation in marmoset hippocampus.

The role of the hippocampus in spatial navigation has been primarily studied in nocturnal mammals, such as rats, that lack many adaptations for daylight vision. Here we demonstrate that during 3D navigation, the common marmoset, a new world primate adapted to daylight, predominantly uses rapid head-gaze shifts for visual exploration while remaining stationary. During active locomotion marmosets stabilize the head, in contrast to rats that use low-velocity head movements to scan the environment as they locomote. Pyramidal neurons in the marmoset hippocampus CA3/CA1 regions predominantly show mixed selectivity for 3D spatial view, head direction, and place. Exclusive place selectivity is scarce. Inhibitory interneurons are predominantly mixed selective for angular head velocity and translation speed. Finally, we found theta phase resetting of local field potential oscillations triggered by head-gaze shifts. Our findings indicate that marmosets adapted to their daylight ecological niche by modifying exploration/navigation strategies and their corresponding hippocampal specializations.

An edge-simplicity bias in the visual input to young infants.

The development of sparse edge coding in the mammalian visual cortex depends on early visual experience. In humans, there are multiple indicators that the statistics of early visual experiences has unique properties that may support these developments. However, there are no direct measures of the edge statistics of infant daily-life experience. Using head-mounted cameras to capture egocentric images of young infants and adults in the home, we found infant images to have distinct edge statistics relative to adults. For infants, scenes with sparse edge patterns-few edges and few orientations-dominate. The findings implicate biased early input at the scale of daily life that is likely specific to the early months after birth and provide insights into the quality, amount, and timing of the visual experiences during the foundational developmental period for human vision.

Primate retina trades single-photon detection for high-fidelity contrast encoding.

How the spike output of the retina enables human visual perception is not fully understood. Here, we address this at the sensitivity limit of vision by correlating human visual perception with the spike outputs of primate ON and OFF parasol (magnocellular) retinal ganglion cells in tightly matching stimulus conditions. We show that human vision at its ultimate sensitivity limit depends on the spike output of the ON but not the OFF retinal pathway. Consequently, nonlinear signal processing in the retinal ON pathway precludes perceptual detection of single photons in darkness but enables quantal-resolution discrimination of differences in light intensity.