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Experimental Eye Research Jun 2024Glaucoma is a neurodegenerative disease characterized by visual field loss associated with optic nerve damage and ocular hypertension. The biological basis for the...
Glaucoma is a neurodegenerative disease characterized by visual field loss associated with optic nerve damage and ocular hypertension. The biological basis for the elevated intraocular pressure (IOP) is largely unknown, such that lowering the IOP is currently the only established treatment. Several animal models have been developed to elucidate the mechanism underlying the increased IOP and for use in drug discovery research, but their utility is often limited by the occurrence of severe intraocular inflammation and by technical challenges. In this study, we developed a rabbit glaucoma model that does not require experimental disease induction. Rabbits were chosen as the model because their eyeballs are similar in size to those of humans, and they are easy to breed. By crossing rabbit strains with inherited glaucoma, as indicated by obvious buphthalmos, we produced a strain that exhibits ocular hypertension. The IOP of the Ocular Hypertension (OH) rabbits was significantly higher than that of the wild type (WT; normal New Zealand white rabbits) from the age of 3 weeks to at least 22 weeks. The significantly larger corneal diameter of the OH rabbits indicated ocular enlargement, whereas there was no significant difference in corneal thickness compared with WT rabbits. Anterior segment ocular coherence tomography and gonioscopic observations revealed an open angle in the OH rabbits. Hematoxylin and eosin (HE) staining together with Masson's trichrome staining showed abnormal collagen accumulation in the angle of the OH rabbit's eyes. Furthermore, aqueous humor (AH) outflow imaging following an intravitreal injection of a fluorescent probe into the anterior chamber for tissue-section analysis revealed retention of the probe in the area of collagen deposition in the OH eyes. The OH rabbits also had a time-dependent increase in the cup/disc ratio. In conclusion, investigations using our newly developed rabbit model of open-angle ocular hypertension showed that abnormal accumulation of extracellular matrix at the angle increased AH outflow resistance in the conventional outflow pathway, leading to a high IOP. Furthermore, the OH rabbits exhibited glaucomatous optic disc cupping over time. These findings suggest the utility of the OH rabbits as a model for open-angle glaucoma (OAG).
PubMed: 38880377
DOI: 10.1016/j.exer.2024.109973 -
NeuroImage Jun 2024A fundamental question in the study of happiness is whether there is neural evidence to support a well-known hypothesis that happy people are always similar while...
A fundamental question in the study of happiness is whether there is neural evidence to support a well-known hypothesis that happy people are always similar while unfortunate people have their own misfortunes. To investigate this, we employed several happiness-related questionnaires to identify potential components of happiness, and further investigated and confirmed their associations with personality, mood, aggressive behaviors, and amygdala reactivity to fearful faces within a substantial sample size of college students (n = 570). Additionally, we examined the functional and morphological similarities and differences among happy individuals using the inter-subject representational similarity analysis (IS-RSA). IS-RSA emphasizes the geometric properties in a high-dimensional space constructed by brain or behavioral patterns and focuses on individual subjects. Our behavioral findings unveiled two factors of happiness: individual and social, both of which mediated the effect of personality traits on individual aggression. Subsequently, mood mediated the impact of happiness on aggressive behaviors across two subgroup splits. Functional imaging data revealed that individuals with higher levels of happiness exhibited reduced amygdala reactivity to fearful faces, as evidenced by a conventional face-matching task (n = 104). Moreover, IS-RSA demonstrated that these participants manifested similar neural activation patterns when processing fearful faces within the visual pathway, but not within the emotional network (e.g., amygdala). Morphological observations (n = 425) indicated that individuals with similar high happiness levels exhibited comparable gray matter volume patterns within several networks, including the default mode network, fronto-parietal network, visual network, and attention network. Collectively, these findings offer early neural evidence supporting the proposition that happy individuals may share common neural characteristics.
PubMed: 38880309
DOI: 10.1016/j.neuroimage.2024.120690 -
Sleep Jun 2024To isolate melanopsin contributions to retinal sensitivity measured by the post-illumination pupil response (PIPR), controlling for individual differences in...
The role of retinal irradiance estimates in melanopsin-driven retinal responsivity: A reanalysis of the post-illumination pupil response (PIPR) in seasonal affective disorder.
To isolate melanopsin contributions to retinal sensitivity measured by the post-illumination pupil response (PIPR), controlling for individual differences in non-melanopsin contributions including retinal irradiance is required. When methodologies to negate such differences present barriers, statistical controls have included age, baseline diameter, iris pigmentation, and circadian time of testing. Alternatively, the pupil light reflex (PLR) and calculations estimating retinal irradiance both reflect retinal irradiance, while the PLR also reflects downstream pathways. We reanalyzed data from an observational, correlational study comparing the PIPR across seasons in seasonal affective disorder (SAD) and controls. The PIPR was measured in 47 adults in Pittsburgh, Pennsylvania (25 SAD) over 50 s after 1 s red and blue stimuli of 15.3 log photons/cm2/s. The PLR was within 1 s while PIPR was averaged over 10-40 seconds post-stimulus. Two raters ranked iris pigmentation using a published scale. We evaluated model fit using Akaike's Information Criterion (AIC) across different covariate sets. The best fitting models included either estimated retinal irradiance or PLR, and circadian time of testing. The PLR is collected contemporaneously in PIPR studies and is an individually specific measure of nonspecific effects, while being minimally burdensome. This work extends the prior publication by introducing theoretically grounded covariates that improved analytic model fits based on AIC specific to the present methods and sample. Such quantitative methods could be helpful in studies which must balance participant and researcher burden against tighter methodological controls of individual differences in retinal irradiance.
PubMed: 38877879
DOI: 10.1093/sleep/zsae109 -
Nano Letters Jun 2024Terahertz scattering scanning near-field optical microscopy is a robust spectral detection technique with a nanoscale resolution. However, there are still major...
Terahertz scattering scanning near-field optical microscopy is a robust spectral detection technique with a nanoscale resolution. However, there are still major challenges in investigating the heterogeneity of cell membrane components in individual cells. Here, we present a novel and comprehensive analytical approach for detecting and investigating heterogeneity in cell membrane components at the single-cell level. In comparison to the resolution of the topographical atomic force microscopy image, the spatial resolution of the terahertz near-field amplitude image is 3 times that of the former. This ultrafine resolution enables the compositional distribution in the cell membrane, such as the distribution of extracellular vesicles, to be finely characterized. Furthermore, via extraction of the near-field absorption images at specific frequencies, the visualization and compositional difference analysis of cell membrane components can be presented in detail. These findings have significant implications for the intuitive and visual analysis of cell development and disease evolutionary pathways.
Topics: Single-Cell Analysis; Cell Membrane; Humans; Terahertz Imaging; Microscopy, Atomic Force; Extracellular Vesicles
PubMed: 38874303
DOI: 10.1021/acs.nanolett.4c01868 -
Cell Genomics Jun 2024Epiretinal membrane (ERM) is a common retinal condition characterized by the presence of fibrocellular tissue on the retinal surface, often with visual distortion and...
Epiretinal membrane (ERM) is a common retinal condition characterized by the presence of fibrocellular tissue on the retinal surface, often with visual distortion and loss of visual acuity. We studied European American (EUR), African American (AFR), and Latino (admixed American, AMR) ERM participants in the Million Veteran Program (MVP) for genome-wide association analysis-a total of 38,232 case individuals and 557,988 control individuals. We completed a genome-wide association study (GWAS) in each population separately, and then results were meta-analyzed. Genome-wide significant (GWS) associations were observed in all three populations studied: 31 risk loci in EUR subjects, 3 in AFR, and 2 in AMR, with 48 in trans-ancestry meta-analysis. Many results replicated in the FinnGen sample. Several GWS variants associate to alterations in gene expression in the macula. ERM showed significant genetic correlation to multiple traits. Pathway enrichment analyses implicated collagen and collagen-adjacent mechanisms, among others. This well-powered ERM GWAS identified novel genetic associations that point to biological mechanisms for ERM.
Topics: Humans; Genome-Wide Association Study; Epiretinal Membrane; Female; Genetic Predisposition to Disease; Male; White People; Polymorphism, Single Nucleotide; Black or African American; Genetic Loci; Aged; United States; Hispanic or Latino; Middle Aged
PubMed: 38870908
DOI: 10.1016/j.xgen.2024.100582 -
Magnetic Resonance in Medical Sciences... Jul 2024Diffusion-weighted MRI (dMRI) provides a unique non-invasive view of human brain tissue properties. The present review article focuses on tractometry analysis methods... (Review)
Review
Diffusion-weighted MRI (dMRI) provides a unique non-invasive view of human brain tissue properties. The present review article focuses on tractometry analysis methods that use dMRI to assess the properties of brain tissue within the long-range connections comprising brain networks. We focus specifically on the major white matter tracts that convey visual information. These connections are particularly important because vision provides rich information from the environment that supports a large range of daily life activities. Many of the diseases of the visual system are associated with advanced aging, and tractometry of the visual system is particularly important in the modern aging society. We provide an overview of the tractometry analysis pipeline, which includes a primer on dMRI data acquisition, voxelwise model fitting, tractography, recognition of white matter tracts, and calculation of tract tissue property profiles. We then review dMRI-based methods for analyzing visual white matter tracts: the optic nerve, optic tract, optic radiation, forceps major, and vertical occipital fasciculus. For each tract, we review background anatomical knowledge together with recent findings in tractometry studies on these tracts and their properties in relation to visual function and disease. Overall, we find that measurements of the brain's visual white matter are sensitive to a range of disorders and correlate with perceptual abilities. We highlight new and promising analysis methods, as well as some of the current barriers to progress toward integration of these methods into clinical practice. These barriers, such as variability in measurements between protocols and instruments, are targets for future development.
Topics: Humans; White Matter; Visual Pathways; Diffusion Tensor Imaging; Brain; Diffusion Magnetic Resonance Imaging; Image Processing, Computer-Assisted; Vision Disorders
PubMed: 38866532
DOI: 10.2463/mrms.rev.2024-0007 -
Cell Reports Jun 2024In addition to its role in vision, light also serves non-image-forming visual functions. Despite clinical evidence suggesting the antipruritic effects of bright light...
In addition to its role in vision, light also serves non-image-forming visual functions. Despite clinical evidence suggesting the antipruritic effects of bright light treatment, the circuit mechanisms underlying the effects of light on itch-related behaviors remain poorly understood. In this study, we demonstrate that bright light treatment reduces itch-related behaviors in mice through a visual circuit related to the lateral parabrachial nucleus (LPBN). Specifically, a subset of retinal ganglion cells (RGCs) innervates GABAergic neurons in the ventral lateral geniculate nucleus and intergeniculate leaflet (vLGN/IGL), which subsequently inhibit CaMKIIα neurons in the LPBN. Activation of both the vLGN/IGL-projecting RGCs and the vLGN/IGL-to-LPBN projections is sufficient to reduce itch-related behaviors induced by various pruritogens. Importantly, we demonstrate that the antipruritic effects of bright light treatment rely on the activation of the retina-vLGN/IGL-LPBN pathway. Collectively, our findings elucidate a visual circuit related to the LPBN that underlies the antipruritic effects of bright light treatment.
Topics: Animals; Mice; Parabrachial Nucleus; Pruritus; Light; Retinal Ganglion Cells; Visual Pathways; Mice, Inbred C57BL; Male; Antipruritics; GABAergic Neurons; Behavior, Animal; Calcium-Calmodulin-Dependent Protein Kinase Type 2
PubMed: 38865246
DOI: 10.1016/j.celrep.2024.114356 -
Molecular Biotechnology Jun 2024Retinal microangiopathies, such as neovascularization and preretinal and vitreous hemorrhages, are the primary pathological features of diabetic retinopathy (DR). These...
Retinal microangiopathies, such as neovascularization and preretinal and vitreous hemorrhages, are the primary pathological features of diabetic retinopathy (DR). These conditions can worsen visual impairment and may result in blindness. Furthermore, multiple metabolic pathways are associated with microangiopathy in DR. However, the specific underlying pathological mechanisms remain unclear. Several studies have demonstrated the important role of G protein-coupled receptor 124 (Gpr124) in cerebral vascular endothelial cells, but its effect on the retinal endothelium has not been elucidated. In this study, we found that Gpr124 is expressed in both pathological retinal fibrous vascular membranes of DR patients and retinal blood vessels of mice, with elevated protein expression specifically observed in the retinas of DR model mice. Furthermore, Gpr124 expression was elevated after high-glucose treatment of human retinal microvascular endothelial cells (HRMECs). Inhibition of Gpr124 expression affected the high glucose-induced proliferation, migration, and tube-forming ability of HRMECs. We concluded that Gpr124 expression was upregulated in DR and promoted HRMECs angiogenesis in a high-glucose environment. This finding may help to elucidate the pathogenesis of DR and provide a critical research basis for identifying effective treatments.
PubMed: 38862861
DOI: 10.1007/s12033-024-01210-w -
Eye (London, England) Jun 2024This article describes the main visual electrodiagnostic tests relevant to neuro-ophthalmology practice, including the visual evoked potential (VEP), and the full-field,... (Review)
Review
This article describes the main visual electrodiagnostic tests relevant to neuro-ophthalmology practice, including the visual evoked potential (VEP), and the full-field, pattern and multifocal electroretinograms (ffERG; PERG; mfERG). The principles of electrophysiological interpretation are illustrated with reference to acquired and inherited optic neuropathies, and retinal disorders that may masquerade as optic neuropathy, including ffERG and PERG findings in cone and macular dystrophies, paraneoplastic and vascular retinopathies. Complementary VEP and PERG recordings are illustrated in demyelinating, ischaemic, nutritional (B12), and toxic (mercury, cobalt, and ethambutol-related) optic neuropathies and inherited disorders affecting mitochondrial function such as Leber hereditary optic neuropathy and dominant optic atrophy. The value of comprehensive electrophysiological phenotyping in syndromic diseases is highlighted in cases of SSBP1-related disease and ROSAH (Retinal dystrophy, Optic nerve oedema, Splenomegaly, Anhidrosis and Headache). The review highlights the value of different electrophysiological techniques, for the purposes of differential diagnosis and objective functional phenotyping.
PubMed: 38862643
DOI: 10.1038/s41433-024-03154-6 -
Nature Communications Jun 2024A brain-computer interface (BCI) enables users to control devices with their minds. Despite advancements, non-invasive BCIs still exhibit high error rates, prompting...
A brain-computer interface (BCI) enables users to control devices with their minds. Despite advancements, non-invasive BCIs still exhibit high error rates, prompting investigation into the potential reduction through concurrent targeted neuromodulation. Transcranial focused ultrasound (tFUS) is an emerging non-invasive neuromodulation technology with high spatiotemporal precision. This study examines whether tFUS neuromodulation can improve BCI outcomes, and explores the underlying mechanism of action using high-density electroencephalography (EEG) source imaging (ESI). As a result, V5-targeted tFUS significantly reduced the error in a BCI speller task. Source analyses revealed a significantly increase in theta and alpha activities in the tFUS condition at both V5 and downstream in the dorsal visual processing pathway. Correlation analysis indicated that the connection within the dorsal processing pathway was preserved during tFUS stimulation, while the ventral connection was weakened. These findings suggest that V5-targeted tFUS enhances feature-based attention to visual motion.
Topics: Humans; Brain-Computer Interfaces; Male; Electroencephalography; Attention; Adult; Female; Young Adult; Visual Cortex; Motion Perception; Photic Stimulation
PubMed: 38862476
DOI: 10.1038/s41467-024-48576-8