Prompted by the title of Ernst Cassirer's 1944 essay, the origin of the idea of a Group theoretical approach, in the mathematical sense, in vision science is here explored, as well as the several ways in which its implementation had been attempted. That object recognition might proceed by a more generative approach rather than by separate individual cataloging had already been argued by Kant, and Cassirer examined how mathematical group theory might be called on for this purpose, in view of the success of its use in geometry and in the physical sciences. However, such a promise appears unlikely in view of the categorical differences between analysis of mental phenomena and of the physical world.

We developed an interactive cortical circuit for visual segmentation that integrates bottom-up and top-down processing to segregate or group visual elements. A bottom-up pathway incorporates stimulus-driven saliency computation, top-down feature-based weighting by relevance and winner-take-all selection. A top-down pathway encompasses multiscale feedback projections, an object-based attention network and a visual segmentation network. Computer simulations have shown that a salient element in the stimulus guides spatial attention and further influences the decomposition of the nearby object into its parts, as postulated by the principle of accentuation. By contrast, when no single salient element is present, top-down feature-based attention highlights all locations occupied by the attended feature and the model forms a Boolean map, i.e., a spatial representation that makes the feature-based grouping explicit. The same distinction between bottom-up and top-down influences in perceptual organization can also be applied to texture perception. The model suggests that the principle of accentuation and feature-based similarity grouping are two manifestations of the same cortical circuit designed to detect similarities and dissimilarities of visual elements in a stimulus.

Glaucoma is a group of optic neuropathies characterised by progressive retinal ganglion cell (RGC) degeneration and is the leading cause of irreversible blindness worldwide. Current treatments for glaucoma focus on reducing intraocular pressure (IOP) with topical medications. However, many patients do not achieve sufficient IOP reductions with such treatments. Patient compliance to dosing schedules also poses a significant challenge, further limiting their effectiveness. While surgical options exist for resistant cases, these are invasive and carry risks of complications. Thus, there is a critical need for better strategies to prevent irreversible vision loss in glaucoma. Gene therapy holds significant promise in this regard, offering potential long-term solutions by targeting the disease's underlying causes at a molecular level. Gene therapy strategies for glaucoma primarily target the two key hallmarks of the disease: elevated IOP and RGC death. This review explores key mechanisms underlying these hallmarks and discusses the current state of gene therapies targeting them. In terms of IOP reduction, this review covers strategies aimed at enhancing extracellular matrix turnover in the conventional outflow pathway, targeting fibrosis, regulating aqueous humor production, and targeting myocilin for gene-specific therapy. Neuroprotective strategies explored include targeting neurotrophic factors and their receptors, reducing oxidative stress and mitochondrial dysfunction, and preventing Wallerian degeneration. This review also briefly highlights key research priorities for advancing gene therapies for glaucoma through the clinical pipeline, such as refining delivery vectors and improving transgene regulation. Addressing these priorities will be essential for translating advancements from preclinical models into effective clinical therapies for glaucoma.

The motion aftereffect (MAE) and motion adaptation in general are usually considered to be universal phenomena. However, in a preliminary study using a bias-free measure of the MAE we found some individuals who showed at best a weak effect of adaptation. These same individuals also performed poorly in a "change detection" test of motion adaptation based on visual search, leading to the conjecture that there is a bimodality in the population with respect to motion adaptation. The present study tested this possibility by screening 102 participants on two versions of the change-detection task while also considering potential confounding factors including eye movements, practice-based improvements, and deficits in visual search ability. The 5 strongest and the 5 weakest change detectors were selected for further testing of motion detection and contrast detection after adaptation. Data showed an inverse association between change-detection ability and performance in the motion-detection task. We extend previous findings by also showing i) the weakest change detectors exhibit less direction selectivity in their contrast thresholds after adapting to drifting gratings and ii) the ability to detect change in motion direction correlates with the ability to detect change in spatial orientation. Group differences between the strongest and weakest change detectors cannot be attributed to a lack of practice, nor can they be explained by poor fixation ability. Our results suggest genuine individual differences in the degree to which adaptation is specific to stimulus orientation and direction of motion.

Increased risk of developing glaucoma has recently been associated with early age of menopause. Here, we examined how age and surgically-induced menopause via ovariectomy (OVX) impacted gene expression in gene pathways previously linked to glaucoma, such as extracellular matrix (ECM) remodeling and TGF-β signaling. Using bulk RNA sequencing, we analyzed changes in young (3-4 months) and middle-aged (9-10 months) Long-Evans rats. We focused on posterior pole tissues (sclera and optic nerve head) but also examined the retina to compare observed changes across different tissue regions. Our results demonstrated that aging and OVX significantly alter gene expression in the sclera and optic nerve head. Generally, OVX triggered the enrichment of immune-related processes. However, OVX in young rats also led to significant enrichment of ECM and TGF-β gene sets. At the same time, these effects were diminished in middle-aged rats, indicating an age dependency of the effects of OVX on matrix-related pathways. Notably, the transcriptional factor Fos was downregulated in the posterior eye and retina in aged and OVX animals. Fos is a major regulator of cell proliferation and survival, and its dysregulation may play an important role in aging and menopause for women. These findings underscore the important role of menopause timing in modulating molecular pathways associated with glaucoma, which is consistent with clinical studies showing that early menopause may heighten the risk of developing this condition. This study also highlights the importance of considering women's health factors, such as menopause, in understanding and managing glaucoma risk.

Bringing objects from peripheral locations to fovea via saccades facilitates their recognition. Human observers integrate pre- and post-saccadic information for recognition. This integration has only been investigated using instructed saccades to prescribed locations. Typically, the target has a fixed pre-saccadic location in an uncluttered scene and is viewed by a pre-determined post-saccadic duration. Consequently, whether trans-saccadic integration is limited or absent when the pre-saccadic target eccentricity is too large in cluttered scenes in unknown. Our study revealed this limit during visual exploration, when observers decided themselves when and to where to make their saccades. We asked thirty observers (400 trials each) to find and report as quickly as possible a target amongst 404 non-targets in an image spanning 57.3°×33.8° in visual angle. We measured the target's pre-saccadic eccentricity e, the duration T of the fixation before the saccade, and the post-saccadic foveal viewing duration T. This T increased with e before starting to saturate around eccentricity e=10°-20°. Meanwhile, T increased much more slowly with e and started decreasing before e. These observations imply the following at sufficiently large pre-saccadic eccentricities: the trans-saccadic integration ceases, target recognition relies exclusively on post-saccadic foveal vision, decision to saccade to the target relies exclusively on target saliency rather than identification. These implications should be applicable to general behavior, although e should depend on object and scene properties. They are consistent with the Central-peripheral Dichotomy that central and peripheral vision are specialized for seeing and looking, respectively.

This focused review highlights the importance of yes-associated protein (YAP)/transcriptional coactivator with PDZ binding motif (TAZ) mechanosignaling in human trabecular meshwork and Schlemm's canal cells in response to glaucoma-associated extracellular matrix stiffening and cyclic mechanical stretch, as well as biochemical pathway modulators (with signaling crosstalk) including transforming growth factor beta 2, glucocorticoids, Wnt, lysophosphatidic acid, vascular endothelial growth factor, and oxidative stress. We provide a comprehensive overview of relevant literature from the last decade, highlight intriguing research avenues with translational potential, and close with an outlook on future directions.

In human visual processing, information from the visual field passes through numerous transformations before perceptual attributes such as motion are derived. Determining the sequence of transforms involved in the perception of visual motion has been an active field since the 1940s. One plausible family of models are the spatiotemporal energy models, based on computations of motion energy computed from the spatiotemporal features the visual field. One of the most venerated is that of Heeger (1988), which hypotheses that motion is estimated by matching the predicted spatiotemporal energy in frequency space. In this study, we investigate the plausibility of Heeger's model by testing for evidence of cortical entrainment to its components. Entrainment of cortical activity to these components was estimated using measurements of electro- and magnetoencephalographic (EMEG) activity, recorded while healthy subjects watched videos of dots moving left and right across their visual field. We find entrainment to several components of Heeger's model bilaterally in occipital lobe regions, including representations of motion energy at a latency of 80 ms, overall velocity at 95 ms, and acceleration at 130 ms. We find little evidence of entrainment to displacement. We contrast Heeger's biologically inspired model with alternative baseline models, finding that Heeger's model provides a closer fit to the observed data. These results help shed light on the processes through which perception of motion arises in the visual processing stream.

A quintessential sentinel of cell health, the membrane potential in nonexcitable cells integrates biochemical and biomechanical inputs, determines the driving force for ionic currents activated by input signals and plays critical functions in cellular differentiation, signaling, and pathology. The identity and properties of ion channels that subserve the resting potential in trabecular meshwork (TM) cells is poorly understood, which impairs our understanding of intraocular pressure regulation in healthy and diseased eyes. Here, we identified a powerful cationic conductance that subserves the TM resting potential. It disappears following Na removal or substitution with choline or NMDG, is insensitive to TTX, verapamil, phenamil methanesulfonate, amiloride and GsMTx4, is substituted by Li and Cs, and inhibited by Gd and Ruthenium Red. Constitutive cation influx is thus not mediated by voltage-operated Na, Ca, epithelial Na (ENaC) channels, Piezo channels or Na/H exchange but may involve TRP-like channels. Transcriptional analysis detected expression of many TRP genes, with the transcriptome pool dominated by TRPC1 followed by expression of TRPV1, TRPC3, TRPV4 and TRPC5. Pyr3 and Pico1,4,5 did not affect the standing current whereas SKF96365 promoted rather than suppressed, Na influx. SEA-0400 induced a modest hyperpolarization, indicating residual contribution from Na/Ca exchange. The resting membrane potential in human TM cells is thus maintained by a constitutive monovalent cation leak current with properties not unlike those of TRP channels. This conductance is likely to influence conventional outflow by setting the homeostatic steady-state and by regulating the magnitude of pressure-induced currents in normotensive and hypertensive eyes.

In visual foraging, foragers collect multiple items from a series of visual displays (or "patches"). When the goal is to maximize the total or the rate of collection of target items, foragers must decide when to leave a depleted patch given that "traveling" from one patch to another incurs a temporal cost. In three experiments, we investigated whether the interposition of a secondary task during travel between patches in visual foraging altered patch-leaving behavior. Over the course of 10- or 30-minute experiments, participants foraged in simulated "berry patches" and traveled to the next patch at will. While they traveled, they either actively performed a secondary task or simply observed passing visual stimuli. Travel time was varied across conditions. The addition of a secondary task, regardless of its relevance to visual foraging, to traveling, or to both, did not impact patch-leaving times in the primary visual foraging task. In Experiment 1 and more weakly in Experiment 2, the patch-leaving decision was based on how long the travel took as predicted by the Marginal Value Theorem (MVT). In Experiment 3, however, patch-leaving did not depend on travel time. Participants 'overharvested' in a manner that suggests that they may have adopted rules different from those of MVT. Across all three experiments, patch-leaving did not depend on the nature of the travel.

Primary open-angle glaucoma (POAG) is a complex, multifactorial disease leading to progressive optic neuropathy and irreversible vision loss. Genome-Wide Association Studies (GWAS) have significantly advanced our understanding of the genetic loci associated with POAG. Expanding on these findings, Exome-Wide Association Studies (ExWAS) refine the genetic landscape by identifying rare coding variants with potential functional relevance. Post-GWAS in silico analyses, including fine-mapping, gene-based association testing, and pathway analysis, offer insights into target genes and biological mechanisms underlying POAG. This review aims to provide a comprehensive roadmap for the post-GWAS characterization of POAG genes. We integrate current knowledge from GWAS, ExWAS, and post-GWAS analyses, highlighting key genetic variants and pathways implicated in POAG. Recent advancements in genomics, such as ATAC-seq, CUT&RUN, and Hi-C, are crucial for identifying disease-relevant gene regulatory elements by profiling chromatin accessibility, histone modifications, and three-dimensional chromatin architecture. These approaches help pinpoint regulatory elements that influence gene expression in POAG. Expression Quantitative Trait Loci (eQTL) analysis and Transcriptome-Wide Association Studies (TWAS) elucidate the impact of these elements on gene expression and disease risk, while functional validations like enhancer reporter assays confirm their relevance. The integration of high-resolution genomics with functional assays and the characterization of genes in vivo using animal models provides a robust framework for unraveling the complex genetic architecture of POAG. This roadmap is essential for advancing our understanding and identification of genes and regulatory networks involved in POAG pathogenesis.

Damage-regulated autophagy modulator 2 (DRAM2) is a homologue of the DRAM family protein, which can induce autophagy process. In the retina, DRAM2 is located to the inner segment of photoreceptors, the apical surface of retinal pigment epithelial (RPE) cells, and the lysosome. Pathogenic variants of DRAM2 lead to autosomal recessive Cone-rod dystrophy 21 (CORD21). Cone-rod dystrophy is characterised by primary cone involvement, or sometimes simultaneous cone and rod loss, thus leading to decreased visual acuity, colour vision deficits, photophobia, and decreased sensitivity of the central visual field. However, the mechanisms underlying DRAM2 related retinal diseases remained unclear. To further explore the role of Dram2 in the retina, we generated Dram2 knockout mice (KO) by CRISPR/Cas-9 technology and demonstrated that expression of DRAM2 was abolished in KO retinas. Dram2 ablation failed to manifest any retinal degenerative phenotypes. Dram2 KO did not exhibit visible defect in photo response and the overt structure of the retinas. Immunostaing analysis using antibodies against cone opsins revealed no detectable loss of cone cells. Moreover, no visible change was observed in the expression and localisation of rhodopsin and other membrane disc proteins in Dram2 KO retinas and no gliosis and apoptosis were detected in KO mice. In summary, these data revealed lack of overt retinal degeneration in Dram2 KO model and emphasized the importance of further investigation of the mechanisms underlying Cone-rod dystrophy 21.

Effective strategies for the neuroprotection and preservation of retinal ganglion cells (RGCs) remain elusive in the management of glaucoma. A spontaneous genetic model of glaucoma has been identified in cats and extensively characterized as a viable translational model, with eye size and anatomy similar to humans. In this study we sought to establish initial proof of concept for gene delivery to feline RGCs via intravitreal injection of AAV2 in normal cats. Pre-retinal, posterior vitreal injection of AAV2/2-CMV-GFP, was performed overlying the area centralis in 5 adult cats. Immunosuppressive oral prednisolone was administered perioperatively and gradually tapered over 6-10wks post-injection. Ophthalmic examination was performed pre- and post-injection. The GFP reporter expression and morphological effects of viral transduction on the retina were monitored in vivo using confocal scanning laser ophthalmoscopy (cSLO) and optical coherence tomography (OCT), respectively (Spectralis OCT-HRA, Heidelberg), at 1-2wk intervals over 6-10wks. Full-field electroretinograms (ERG) and visual evoked potentials (VEP) were recorded at baseline and post-injection. Retinas were examined by histology and immunolabeling for the RGC marker RBPMS and Müller cell and astrocyte marker SOX9, and GFP expression was examined in the retina, optic nerve (ON), optic tract and lateral geniculate nucleus (LGN). GFP retinal cells and RGC axons were visualized by cSLO at 1-2 weeks post-injection. No retinal morphological changes were observed by OCT in vivo but 3/5 eyes exhibited mild retinal inflammation on histology. Retinal and ON function were preserved in injected eyes compared to baseline and untreated eyes. GFP expression was predominantly identified in RBPMS RGC cells as well as SOX9 Müller cells. GFP fluorescence was observed throughout RGC nerve fiber tract in the central visual pathway. Peak transduction in RGCs (up to ∼ 20 %) was observed in the regions with high GFP expression, but < 1 % of RGCs expressed GFP across the whole retina. Our data provide proof of concept that pre-retinal injection of AAV2/2 may represent a feasible platform for gene delivery to feline RGCs in vivo but highlight a need for further refinement to improve RGC transduction efficiency and control low-grade retinal inflammation.

Exfoliation syndrome (XFS), or pseudoexfoliation syndrome, is considered a systemic disorder that leads to glaucoma with progressive visual field loss. A better insight into the underlying pathogenic mechanism will help diagnose the disease and prevent and slow progression. Here, we provide an overview of disease pathogenesis in the light of GWAS and multi-omics research. We discuss possible environmental interactions related to XFS. We investigate the potential interactions in differentially expressed genes from RNA-Seq by using Ingenuity Pathway Analysis. MAPK pathway was identified as the top network of these genes. Further investigation is needed to verify our results in vivo. It is necessary to establish an animal model mimicking exfoliation syndrome phenotypes.

Spatial cues have previously been found to facilitate information processing not only at cued locations but also within cued objects, so-called object-based attention. We used different variants of the classic two-rectangle paradigm to investigate the interaction of cue location and object orientation on object-based attentional effects. First, we re-analyzed data from a prior study using the classical two-rectangle paradigm. We expected faster attentional shifts along the horizontal compared to the vertical meridian. Results confirmed that cue location and rectangle orientation interactively influence object-based attention, with horizontal objects combined with upper left visual field cues eliciting faster responses than other conditions. In Experiment 2, we removed object contours to examine the benefits of shifting attention based purely on cue location. The results showed that these differences remained, indicating that attentional shifts are not solely guided by object contours. In Experiment 3, we added a third possible target location to the original two-rectangle experiment to examine whether attentional shifts followed a predictable pattern across the stimulus display. Despite faster responses to cued targets, no consistent and organized visual search pattern was observed when participants searched for targets at invalidly cued locations. Our findings suggest that object-based effects are influenced by both cue location and the orientation of attentional shifts. Shifts from left to right in the upper visual field consistently demonstrated significant benefits, whereas the benefits of vertical shifts were less consistent across experiments.

Flickering patterns that shift in chromaticity can be uncomfortable and may trigger epileptic seizures, though the underlying factors are not fully understood. In the spatial domain, chromatic contrast in images is a potential predictor of visual discomfort, with higher contrast generally leading to increased discomfort. This study investigated whether chromatic contrast between two flickering colors in a uniform field influences discomfort. Participants rated their subjective discomfort for various flickering color combinations defined by the CIE L*a*b* uniform color space. Overall, discomfort increased with both chromatic and brightness contrasts. Additionally, flickers containing highly saturated red generally caused greater discomfort compared to those without red, an effect not observed with low saturation. Our findings suggest that visual discomfort induced by time-varying chromatic patterns is partly influenced by chromatic contrast over time. Furthermore, unlike the spatial domain, discomfort in the temporal domain may be specifically associated with the hue of red.

In recent years, extracellular vesicles (EVs) have attracted significant scientific interest due to their widespread distribution, their potential as disease biomarkers, and their promising applications in therapy. Encapsulated by lipid bilayers these nanovesicles include small extracellular vesicles (sEV) (30-150 nm), microvesicles (100-1000 nm), and apoptotic bodies (100-5000 nm) and are essential for cellular communication, immune responses, biomolecular transport, and physiological regulation. As they reflect the condition and functionality of their originating cells, EVs play critical roles in numerous physiological processes and diseases. Therefore, EVs offer valuable opportunities for uncovering disease mechanisms, enhancing drug delivery systems, and identifying novel biomarkers. In the context of glaucoma, a leading cause of irreversible blindness, the specific roles of EVs are still largely unexplored. This review examines the emerging role of EVs in the pathogenesis of glaucoma, with a focus on their potential as diagnostic biomarkers and therapeutic agents. Through a thorough analysis of current literature, we summarize key advancements in EV research and identify areas where further investigation is needed to fully understand their function in glaucoma.

There is currently a diverse array of treatment for amblyopia. In addition to the traditional penalization therapy, which has been used for over 200 years, there are not only more active treatments to recover the monocular visual loss of the amblyopic eye involving both behavioral (visual training) as well as non-invasive brain stimulation but also a variety of methods designed specifically to restore binocular function. Our understanding of visual function in general and of the etiology of the amblyopic loss in particular has progressed a great deal over the last 50 years and it is now time to take a more principled approach to how we treat, when we treat and why we treat.

Viewing a rapid sequence of face images shown in the periphery can lead to large caricature-like distortions in the perceived images, a phenomenon known as the Flashed Face Distortion Effect (FFDE). The mechanisms underlying FFDE are poorly understood. Here we examined the timing and sites of the adaptation processes giving rise to the FFDE. To investigate the effects of presentation rate, we maintained consistent trial lengths while assessing how variations in the temporal frequencies of face presentation influenced the magnitude of face distortion and the averaging of facial expressions. Over a wide range of temporal frequencies (1.2-60 Hz) tested, we observed a decrease in FFDE strength as the presentation rate increased. To probe the neural sites of FFDE, we varied whether successive faces were presented to the same or different eyes using a dichoptic display. Distortion effects were comparable for monocular, binocular, and interocular conditions, yet much larger than a control condition where faces were presented with a temporal interval between successive images, suggesting a cortical locus for FFDE.

Previous studies identified two visual stimuli that can shorten the human eye by thickening the choroid after short-term visual stimulation, potentially inhibiting myopia: (1) watching digitally filtered movies where the red plane has full spatial resolution while green and blue are low-pass filtered according to the human longitudinal chromatic aberration (LCA) function (the "red in focus" filter), and (2) reading text with inverted contrast. This study aimed to determine whether combining these two stimuli would have an additive effect on axial length. Twenty-two emmetropic subjects were recruited to read text (standard and inverted contrast) for 30 min from a large screen, 2 m away, either unfiltered or filtered with the "red in focus" filter. Axial length was measured before and after each reading episode using low-coherence interferometry (Lenstar LS 900, Haag Streit). Reading text with conventional contrast polarity (dark letters on a bright background) resulted in no significant axial length change. Adding the "red in focus" filter did not alter the outcome. Consistent with previous findings, reading inverted contrast text made emmetropic eyes shorter. Surprisingly, when the text was combined with the "red in focus" filter, eyes became longer rather than shorter. A possible explanation for this contradictory result is that, for the text stimulus, the "red in focus" filter removes spatial information in the blue channel needed by the retina to use LCA analysis to thicken the choroid.

The receptive field (RF) is the fundamental processing unit of human vision; both masking and crowding depend on its size. The RF has a psychophysical corresponding term, the perceptive field (PF); whereas the RF is measured physiologically, the PF is measured psychophysically (a perceptual response). We investigated how spatial (lateral interactions), temporal (the stimulus presentation time), and the procedure affect the PF size for both monocular and binocular viewing. The stimuli consisted of a central vertically oriented Gabor target and high-contrast Gabor flankers positioned in two configurations (orthogonal or collinear) with target-flanker separations of either 2 or 3 wavelengths (λ). We used two main methods to control the monocular and binocular vision: mono-optic glasses vs. stereo glasses. The presentation order was either mixed or non-mixed for the presentation time and the eye condition. We estimated the PF size for both monocular and binocular viewing at 4 different presentation times (40, 80,120, and 200 ms) with different orders of presentation in each experiment (mono-optic glasses vs. stereo glasses, utilizing the lateral masking paradigm). In each experiment we explored one variable: how changing one parameter would affect the PF size in both monocular and binocular viewing (the temporal duration, the testing order of conditions, and the spatial distance) while keeping the others constant. We found that both the monocular and binocular PF size were dynamic and were significantly affected by the presentation order, leading to reduced lateral suppression under the collinear 2λ condition. Hence, both the monocular and binocular PF size depended on the sequence of the stimulus presentation time and the testing order of the conditions. Furthermore, we found that the binocular PF size was significantly larger than the monocular PF size.

Contrast demodulation and phase distortions are exaggerated in retinal images blurred by the higher-order wavefront aberrations of keratoconic eyes. While the performance loss from the former parameter is well understood, little is known about the impact of the latter on visual functions in this disease condition. The present study investigated the impact of phase distortions on the monocular logMAR visual acuity, letter discriminability and random-dot stereoacuity of seventeen visually healthy adults (ten for visual acuity and letter discriminability; ten for stereoacuity and three common to both experiments) using images that were computationally blurred by four different higher-order wavefront aberration profiles of keratoconic eyes that showed significant distortions in the phase spectrum. Participants viewed these images through 2 mm artificial pupils to negate their native ocular wavefront aberrations. The results showed progressive losses in visual acuity and stereoacuity with increasing blur, a third of which could be recovered following phase nullification. Letter discriminability also improved following phase nullification, more so for smaller than larger optotypes. Stereoacuity loss and, consequently, its recovery following phase nullification was more prominent for profiles simulating unilateral asymmetric keratoconus than for profiles simulating bilateral symmetric keratoconus. These results agree with previous reports obtained from blur induced with lower-order aberrations and indicate that a similar trend may be observed for more complex patterns of blur like keratoconus. Overall, both contrast demodulation and misalignment of the local features of the blurred image may contribute to losses of spatial and depth vision in keratoconus. Phase nullification may partially mitigate these losses, thereby allowing the processing of finer spatial details and veridical disparity estimations for improved depth perception.

Sensory neurons often encode multisensory or multimodal signals. For example, many medial superior temporal (MST) neurons are tuned to heading direction of self-motion based on visual (optic flow) signals and vestibular signals. Middle temporal (MT) cortical neurons are tuned to object depth from signals of two visual modalities: motion parallax and binocular disparity. A MST neuron's preferred heading directions from different senses can be congruent (matched) or opposite from each other. Similarly, the preferred depths of a MT neuron from the two modalities are congruent in some neurons and opposite in other neurons. While the congruent tuning appears natural for cue integration, the functions of the opposite tuning have been puzzling. This paper explains these tunings from the efficient coding principle that sensory encoding extracts as much sensory information as possible while minimizing neural cost. It extends the previous applications of this principle to understand neural receptive fields in retina and the primary visual cortex, particularly multimodal encoding of cone signals or binocular signals. Congruent and opposite sensory signals that excite the congruent and opposite neurons, respectively, are the decorrelated sensory components that provide a general purpose, efficient, representation of sensory inputs before task specific object segmentation and recognition. It can be extended to encoding signals from more than two sensory sources, e.g., from three cone types. This framework also predicts a wider tuning width for the opposite than congruent neurons, neurons that are neither congruent nor opposite, and how neural receptive fields adapt to statistical changes of sensory environments.

Many of the objects we encounter in our everyday environments would be hard to recognize without any expectations about these objects. For example, a distant silhouette may be perceived as a car because we expect objects of that size, positioned on a road, to be cars. Reflecting the influence of such expectations on visual processing, neuroimaging studies have shown that when objects are poorly visible, expectations derived from scene context facilitate the representations of these objects in visual cortex from around 300 ms after scene onset. The current magnetoencephalography (MEG) study tested whether this facilitation occurs independently of attention and task relevance. Participants viewed degraded objects alone or within scene context while they either attended the scenes (attended condition) or the fixation cross (unattended condition), also temporally directing attention away from the scenes. Results showed that at 300 ms after stimulus onset, multivariate classifiers trained to distinguish clearly visible animate vs inanimate objects generalized to distinguish degraded objects in scenes better than degraded objects alone, despite the added clutter of the scene background. Attention also modulated object representations at this latency, with better category decoding in the attended than the unattended condition. The modulatory effects of context and attention were independent of each other. Finally, data from the current study and a previous study were combined (N = 51) to provide a more detailed temporal characterization of contextual facilitation. These results extend previous work by showing that facilitatory scene-object interactions are independent of the specific task performed on the visual input.

Binocular disparity provides information about the depth structure of objects and surfaces in our environment. Since disparity depends on the distance to objects as well as the depth separation of points, information about distance is required to estimate depth from disparity. Our perception of size and shape is biased, such that far objects appear too small and flattened in depth, and near objects too big and stretched in depth. The current study assessed the extent to which the failure of depth constancy can be accounted for by the uncertainty of distance information provided by vergence. We measured individual differences in vergence noise using a nonius line task, and the degree of depth constancy using a task in which observers judged the magnitude of a depth interval relative to the vertical distance between two targets in the image plane. We found no correlation between the two measures, and show that depth constancy was much poorer than would be expected from vergence noise measured in this way. This limited ability to take account of vergence in the perception of depth is, however, consistent with our poor sensitivity to absolute disparity differences. This absolute disparity anomaly thus also applies to our poor ability to make use of vergence information for absolute distance judgements.

Glaucoma is a leading cause of blindness worldwide and glaucoma patients exhibit an early diffuse loss of retinal sensitivity followed by focal loss of RGCs. Combining some previous published results and some new data, this paper provides our current view on how high IOP (H-IOP) affects the light response sensitivity of a subset of RGCs, the alpha-ganglion cells (αGCs), as well as their presynaptic bipolar cells (DBCs and HBCs) and A2 amacrine cells (AIIACs) in dark-adapted mouse retinas. Our data demonstrate that H-IOP in experimental glaucoma mice significantly decreases light-evoked spike response sensitivity of sONαGCs and sOFFαGCs (i.e., raises thresholds by 1.5-2.5 log units), but not that of the tONαGCs and tOFFαGCs. The sensitivity loss in sONαGCs and sOFFαGCs is mediated by a H-IOP induced suppression of AIIAC response which is caused by a decrease of transmission efficacy of the DBC→AIIAC synapse. We also provide evidence supporting the hypothesis that BK channels in the A17AC→DBC feedback synapse are the H-IOP sensor that regulates the DBC→AIIAC synaptic efficacy, as BK channel blocker IBTX mimics the action of H-IOP. Our results provide useful information for designing strategies for early detection and possible treatments of glaucoma as physiological changes occur before irreversible structural damage.

Glaucoma is a leading cause of irreversible blindness worldwide. The most common form, primary open-angle glaucoma (POAG), is a genetically complex trait with high heritability. Genome-wide association studies have identified significant POAG and IOP association of a genomic region on chromosome 12 that includes ATXN2 as well as 7 other genes. Association of protein disrupting ATXN2 variants in the NEIGHBORHOOD case-control cohort and the UK Biobank suggests that ATXN2 is a key gene in this locus. To investigate functional effects, we utilized a zebrafish (Danio rerio) CRISPR/Cas9 edited atxn2-knockdown line to show that loss of atxn2 results in reduced eye size, diminished retinal ganglion cells (RGC), increased intraocular pressure (IOP), and impaired visual function in zebrafish. Complementation assays supported functional effects for 14 POAG-associated human ATXN2 missense variants. These results suggest a loss-of-function mechanism underlying a potential role for ATXN2 in POAG pathogenesis.

Optineurin (OPTN) is a gene associated with familial normal tension glaucoma (NTG). While NTG involves intraocular pressure (IOP)-independent neurodegeneration of the visual pathway that progresses with age, how OPTN dysfunction leads to NTG remains unclear. Here, we generated an OPTN knockout mouse (Optn) model to test the hypothesis that a loss-of-function mechanism induces structural and functional eye deterioration with aging. Eye anatomy, visual function, IOP, retinal histology, and retinal ganglion cell survival were compared to littermate wild-type (WT) control mice. Consistent with OPTN's role in NTG, loss of OPTN did not increase IOP or alter gross eye anatomy in young (2-3 months) or aged (12 months) mice. When retinal layers were quantitated, young Optn mice had thinner retina in the peripheral regions than young WT mice, primarily due to thinner ganglion cell-inner plexiform layers. Despite this, visual function in Optn mice was not severely impaired, even with aging. We also assessed relative abundance of retinal cell subtypes, including amacrine cells, bipolar cells, cone photoreceptors, microglia, and astrocytes. While many of these cellular subtypes were unaffected by Optn deletion, more dopaminergic amacrine cells were observed in aged Optn mice. Taken together, our findings showed that complete loss of Optn resulted in mild retinal changes and less visual function impairment, supporting the possibility that OPTN-associated glaucoma does not result from a loss-of-function disease mechanism. Further research using these Optn mice will elucidate detailed molecular pathways involved in NTG and identify clinical or environmental risk factors that can be targeted for glaucoma treatment.

Reading on mobile phones can cause visual discomfort, negatively affecting visual health. Most studies have focused on neutral text-background combinations, with limited validation for coloured text-background combinations. This study investigates the impact of coloured text on neutral backgrounds and the colour difference between text and background on visual comfort during digital reading. A psychophysical experiment was conducted, where 230 images of coloured text on neutral backgrounds were evaluated by 20 participants using a 6-point scale for visual comfort. Results showed that reading coloured text on a black background generally provided higher comfort compared to a white background. Additionally, visual comfort decreased as the text colour approached that of the background. The effect of text hue on comfort was not significant. Furthermore, several visual comfort models for mobile displays were developed and compared. The VC model is based on Bern's attributes, while the VC model focuses on the lightness of text and background. The VC model includes both lightness and chroma attributes. Comparisons revealed that VC outperformed the others in predicting visual comfort, highlighting the importance of lightness and chroma in improving predictive accuracy. Therefore, the VC model is useful for evaluating the visual comfort of coloured text on neutral backgrounds.