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Neurology(R) Neuroimmunology &... May 2024Optic neuritis is the most common optic neuropathy in young adults and a frequent manifestation of multiple sclerosis. Its clinical course is pertinent to the design of... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND AND OBJECTIVES
Optic neuritis is the most common optic neuropathy in young adults and a frequent manifestation of multiple sclerosis. Its clinical course is pertinent to the design of visual pathway neuroprotection trials.
METHODS
This is a secondary analysis of longitudinal data from the TONE trial, which included 103 patients from 12 German academic tertiary centers with acute unilateral optic neuritis as a clinically isolated syndrome and baseline high-contrast visual acuity <0.5 decimal. Patients were randomized to 1,000 mg methylprednisolone i.v./d plus either erythropoietin (33,000 IU/d) or placebo (saline solution) for 3 days. They were followed up at standardized intervals with a battery of tests including high-contrast visual acuity, low-contrast letter acuity, contrast sensitivity, visual fields, visual evoked potentials, and retinal optical coherence tomography. At 6 months, participants answered a standardized questionnaire on vision-related quality of life (NEI-VFQ 25). We describe the disease course with mixed-effects piecewise linear models and calculate structure-function correlations using Pearson r. Because erythropoietin had no effect on the visual system, we use pooled (treatment-agnostic) data.
RESULTS
Patients experienced initial rapid and then decelerating improvements of visual function with thinning of inner and thickening of outer retinal layers. At 6 months, visual parameters were positively correlated with inner and negatively correlated with outer retinal thickness changes. Peripapillary retinal nerve fiber layer thinning predominantly occurred in sectors without previous swelling. At 6 months, macular ganglion cell and inner plexiform layer thinning was weakly correlated with the P100 peak time (r = -0.11) and moderately correlated with the amplitude of visual evoked potentials (r = 0.35). Only functional outcomes were at least moderately correlated with vision-related quality of life.
DISCUSSION
The longitudinal data from this large study cohort may serve as a reference for the clinical course of acute optic neuritis. The pattern of correlation between visual evoked potentials and inner retinal thinning may argue that the latter is mostly due to ganglion cell loss, rather than dysfunction. Visual pathway neuroprotection trials with functional outcomes are needed to confirm that candidate drugs will benefit patients' vision-related quality of life.
TRIAL REGISTRATION INFORMATION
ClinicalTrials.gov, NCT01962571.
Topics: Humans; Young Adult; Disease Progression; Erythropoietin; Evoked Potentials, Visual; Optic Neuritis; Quality of Life
PubMed: 38588480
DOI: 10.1212/NXI.0000000000200223 -
Current Biology : CB Nov 2023Early visual areas are retinotopically organized in human and non-human primates. Population receptive field (pRF) size increases with eccentricity and from lower- to...
Early visual areas are retinotopically organized in human and non-human primates. Population receptive field (pRF) size increases with eccentricity and from lower- to higher-level visual areas. Furthermore, the cortical magnification factor (CMF), a measure of how much cortical space is devoted to each degree of visual angle, is typically larger for foveal as opposed to peripheral regions of the visual field. Whether this fine-scale organization within and across visual areas depends on early visual experience has yet been unknown. Here, we employed 7T functional magnetic resonance imaging pRF mapping to assess the retinotopic organization of early visual regions (i.e., V1, V2, and V3) in eight sight recovery individuals with a history of congenital blindness until a maximum of 4 years of age. Compared with sighted controls, foveal pRF sizes in these individuals were larger, and pRF sizes did not show the typical increase with eccentricity and down the visual cortical processing stream (V1-V2-V3). Cortical magnification was overall diminished and decreased less from foveal to parafoveal visual field locations. Furthermore, cortical magnification correlated with visual acuity in sight recovery individuals. The results of this study suggest that early visual experience is essential for refining a presumably innate prototypical retinotopic organization in humans within and across visual areas, which seems to be crucial for acquiring full visual capabilities.
Topics: Animals; Humans; Brain Mapping; Visual Fields; Visual Perception; Visual Cortex; Vision, Ocular; Magnetic Resonance Imaging; Visual Pathways
PubMed: 37918397
DOI: 10.1016/j.cub.2023.10.010 -
Molecular Medicine Reports Sep 2023The degeneration of retinal ganglion cells (RGCs) often causes irreversible vision impairment. Prevention of RGC degeneration can prevent or delay the deterioration of...
The degeneration of retinal ganglion cells (RGCs) often causes irreversible vision impairment. Prevention of RGC degeneration can prevent or delay the deterioration of visual function. The present study aimed to investigate retinal metabolic profiles following optic nerve transection (ONT) injury and identify the potential metabolic targets for the prevention of RGC degeneration. Retinal samples were dissected from ONT group and non‑ONT group. The untargeted metabolomics were carried out using liquid chromatography‑tandem mass spectrometry. The involved pathways and biomarkers were analyzed using Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and MetaboAnalyst 5.0. In the ONT group, 689 disparate metabolites were detected, including lipids and lipid‑like molecules. A total of 122 metabolites were successfully annotated and enriched in 50 KEGG pathways. Among them, 'sphingolipid metabolism' and 'primary bile acid biosynthesis' were identified involved in RGC degeneration. A total of five metabolites were selected as the candidate biomarkers for detecting RGC degeneration with an AUC value of 1. The present study revealed that lipid‑related metabolism was involved in the pathogenesis of retinal neurodegeneration. Taurine, taurochenodesoxycholic acid, taurocholic acid (TCA), sphingosine, and galabiosylceramide are shown as the promising biomarkers for the diagnosis of RGC degeneration.
Topics: Humans; Optic Nerve Injuries; Optic Nerve; Retina; Metabolomics; Biomarkers; Lipids
PubMed: 37539744
DOI: 10.3892/mmr.2023.13065 -
Brain Sciences Sep 2023Rapid eye movement (REM) sleep is the main sleep correlate of dreaming. Ponto-geniculo-occipital (PGO) waves are a signature of REM sleep. They represent the... (Review)
Review
Rapid eye movement (REM) sleep is the main sleep correlate of dreaming. Ponto-geniculo-occipital (PGO) waves are a signature of REM sleep. They represent the physiological mechanism of REM sleep that specifically limits the processing of external information. PGO waves look just like a message sent from the pons to the lateral geniculate nucleus of the visual thalamus, the occipital cortex, and other areas of the brain. The dedicated visual pathway of PGO waves can be interpreted by the brain as visual information, leading to the visual hallucinosis of dreams. PGO waves are considered to be both a reflection of REM sleep brain activity and causal to dreams due to their stimulation of the cortex. In this review, we summarize the role of PGO waves in potential neural circuits of two major theories, i.e., (1) dreams are generated by the activation of neural activity in the brainstem; (2) PGO waves signaling to the cortex. In addition, the potential physiological functions during REM sleep dreams, such as memory consolidation, unlearning, and brain development and plasticity and mood regulation, are discussed. It is hoped that our review will support and encourage research into the phenomenon of human PGO waves and their possible functions in dreaming.
PubMed: 37759951
DOI: 10.3390/brainsci13091350 -
Brain Sciences Oct 2023Optic pathway glioma (OPG) is one of the causes of pediatric visual impairment. Unfortunately, there is as yet no cure for such a disease. Understanding the underlying... (Review)
Review
Optic pathway glioma (OPG) is one of the causes of pediatric visual impairment. Unfortunately, there is as yet no cure for such a disease. Understanding the underlying mechanisms and the potential therapeutic strategies may help to delay the progression of OPG and rescue the visual morbidities. Here, we provide an overview of preclinical OPG studies and the regulatory pathways controlling OPG pathophysiology. We next discuss the role of microenvironmental cells (neurons, T cells, and tumor-associated microglia and macrophages) in OPG development. Last, we provide insight into potential therapeutic strategies for treating OPG and promoting axon regeneration.
PubMed: 37891793
DOI: 10.3390/brainsci13101424 -
International Journal of Molecular... Nov 2023Diabetic retinopathy (DR) is renowned as a leading cause of visual loss in working-age populations with its etiopathology influenced by the disturbance of biochemical... (Review)
Review
Diabetic retinopathy (DR) is renowned as a leading cause of visual loss in working-age populations with its etiopathology influenced by the disturbance of biochemical metabolic pathways and genetic factors, including gene polymorphism. Metabolic pathways considered to have an impact on the development of the disease, as well as genes and polymorphisms that can affect the gene expression, modify the quantity and quality of the encoded product (protein), and significantly alter the metabolic pathway and its control, and thus cause changes in the functioning of metabolic pathways. In this article, the screening of chromosomes and the most important genes involved in the etiology of diabetic retinopathy is presented. The common databases with manuscripts published from January 2000 to June 2023 have been taken into consideration and chosen. This article indicates the role of specific genes in the development of diabetic retinopathy, as well as polymorphic changes within the indicated genes that may have an impact on exacerbating the symptoms of the disease. The collected data will allow for a broader look at the disease and help to select candidate genes that can become markers of the disease.
Topics: Humans; Diabetic Retinopathy; Polymorphism, Genetic; Diabetes Mellitus, Type 2
PubMed: 37958858
DOI: 10.3390/ijms242115865 -
Nature Communications Nov 2023In the mammalian visual system, the ventral lateral geniculate nucleus (vLGN) of the thalamus receives salient visual input from the retina and sends prominent GABAergic...
In the mammalian visual system, the ventral lateral geniculate nucleus (vLGN) of the thalamus receives salient visual input from the retina and sends prominent GABAergic axons to the superior colliculus (SC). However, whether and how vLGN contributes to fundamental visual information processing remains largely unclear. Here, we report in mice that vLGN facilitates visually-guided approaching behavior mediated by the lateral SC and enhances the sensitivity of visual object detection. This can be attributed to the extremely broad spatial integration of vLGN neurons, as reflected in their much lower preferred spatial frequencies and broader spatial receptive fields than SC neurons. Through GABAergic thalamocollicular projections, vLGN specifically exerts prominent surround suppression of visuospatial processing in SC, leading to a fine tuning of SC preferences to higher spatial frequencies and smaller objects in a context-dependent manner. Thus, as an essential component of the central visual processing pathway, vLGN serves to refine and contextually modulate visuospatial processing in SC-mediated visuomotor behaviors via visually-driven long-range feedforward inhibition.
Topics: Mice; Animals; Geniculate Bodies; Neurons; Thalamus; Visual Pathways; Superior Colliculi; Mammals
PubMed: 37949869
DOI: 10.1038/s41467-023-43147-9 -
Cell Research Mar 2024Flickering light stimulation has emerged as a promising non-invasive neuromodulation strategy to alleviate neuropsychiatric disorders. However, the lack of a...
Flickering light stimulation has emerged as a promising non-invasive neuromodulation strategy to alleviate neuropsychiatric disorders. However, the lack of a neurochemical underpinning has hampered its therapeutic development. Here, we demonstrate that light flickering triggered an immediate and sustained increase (up to 3 h after flickering) in extracellular adenosine levels in the primary visual cortex (V1) and other brain regions, as a function of light frequency and intensity, with maximal effects observed at 40 Hz frequency and 4000 lux. We uncovered cortical (glutamatergic and GABAergic) neurons, rather than astrocytes, as the cellular source, the intracellular adenosine generation from AMPK-associated energy metabolism pathways (but not SAM-transmethylation or salvage purine pathways), and adenosine efflux mediated by equilibrative nucleoside transporter-2 (ENT2) as the molecular pathway responsible for extracellular adenosine generation. Importantly, 40 Hz (but not 20 and 80 Hz) light flickering for 30 min enhanced non-rapid eye movement (non-REM) and REM sleep for 2-3 h in mice. This somnogenic effect was abolished by ablation of V1 (but not superior colliculus) neurons and by genetic deletion of the gene encoding ENT2 (but not ENT1), but recaptured by chemogenetic inhibition of V1 neurons and by focal infusion of adenosine into V1 in a dose-dependent manner. Lastly, 40 Hz light flickering for 30 min also promoted sleep in children with insomnia by decreasing sleep onset latency, increasing total sleep time, and reducing waking after sleep onset. Collectively, our findings establish the ENT2-mediated adenosine signaling in V1 as the neurochemical basis for 40 Hz flickering-induced sleep and unravel a novel and non-invasive treatment for insomnia, a condition that affects 20% of the world population.
Topics: Humans; Child; Animals; Mice; Sleep Initiation and Maintenance Disorders; Sleep; Signal Transduction; Adenosine; Astrocytes
PubMed: 38332199
DOI: 10.1038/s41422-023-00920-1