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Neural Regeneration Research Oct 2024JOURNAL/nrgr/04.03/01300535-202410000-00031/figure1/v/2024-02-06T055622Z/r/image-tiff Glutamate excitotoxicity has been shown to play an important role in glaucoma, and...
JOURNAL/nrgr/04.03/01300535-202410000-00031/figure1/v/2024-02-06T055622Z/r/image-tiff Glutamate excitotoxicity has been shown to play an important role in glaucoma, and glutamate can induce ferroptosis. The p38 mitogen-activated protein kinase (MAPK) pathway inhibitor SB202190 has a potential ability to suppress ferroptosis, and its downstream targets, such as p53, have been shown to be associated with ferroptosis. However, whether ferroptosis also occurs in retinal ganglion cells in response to glutamate excitotoxicity and whether inhibition of ferroptosis reduces the loss of retinal ganglion cells induced by glutamate excitotoxicity remain unclear. This study investigated ferroptosis in a glutamate-induced glaucoma rat model and explored the effects and molecular mechanisms of SB202190 on retinal ganglion cells. A glutamate-induced excitotoxicity model in R28 cells and an N-methyl-D-aspartate-induced glaucoma model in rats were used. In vitro experiments showed that glutamate induced the accumulation of iron and lipid peroxide and morphological changes of mitochondria in R28 cells, and SB202190 inhibited these changes. Glutamate induced the levels of p-p38 MAPK/p38 MAPK and SAT1 and decreased the expression levels of ferritin light chain, SLC7A11, and GPX4. SB202190 inhibited the expression of iron death-related proteins induced by glutamate. In vivo experiments showed that SB202190 attenuated N-methyl-D-aspartate-induced damage to rat retinal ganglion cells and improved visual function. These results suggest that SB202190 can inhibit ferroptosis and protect retinal ganglion cells by regulating ferritin light chain, SAT1, and SLC7A11/Gpx4 pathways and may represent a potential retina protectant.
PubMed: 38488564
DOI: 10.4103/1673-5374.391193 -
Redox Biology Nov 2023Excessive light exposure can damage photoreceptors and lead to blindness. Oxidative stress serves a key role in photo-induced retinal damage. Free radical scavengers...
Excessive light exposure can damage photoreceptors and lead to blindness. Oxidative stress serves a key role in photo-induced retinal damage. Free radical scavengers have been proven to protect against photo-damaged retinal degeneration. Fullerol, a potent antioxidant, has the potential to protect against ultraviolet-B (UVB)-induced cornea injury by activating the endogenous stem cells. However, its effects on cell fate determination of Müller glia (MG) between gliosis and de-differentiation remain unclear. Therefore, we established a MG lineage-tracing mouse model of light-induced retinal damage to examine the therapeutic effects of fullerol. Fullerol exhibited superior protection against light-induced retinal injury compared to glutathione (GSH) and reduced oxidative stress levels, inhibited gliosis by suppressing the TGF-β pathway, and enhanced the de-differentiation of MG cells. RNA sequencing revealed that transcription candidate pathways, including Nrf2 and Wnt10a pathways, were involved in fullerol-induced neuroprotection. Fullerol-mediated transcriptional changes were validated by qPCR, Western blotting, and immunostaining using mouse retinas and human-derived Müller cell lines MIO-M1 cells, confirming that fullerol possibly modulated the Nrf2, Wnt10a, and TGF-β pathways in MG, which suppressed gliosis and promoted the de-differentiation of MG in light-induced retinal degeneration, indicating its potential in treating retinal diseases.
Topics: Animals; Mice; Humans; Ependymoglial Cells; Retinal Degeneration; Gliosis; NF-E2-Related Factor 2; Retina; Neuroglia; Transforming Growth Factor beta
PubMed: 37816275
DOI: 10.1016/j.redox.2023.102911 -
Vision (Basel, Switzerland) May 2024Neurofibromatosis type 1 (NF1) is an inherited autosomal dominant disorder primarily affecting children and adolescents characterized by multisystemic clinical... (Review)
Review
Neurofibromatosis type 1 (NF1) is an inherited autosomal dominant disorder primarily affecting children and adolescents characterized by multisystemic clinical manifestations. Mutations in neurofibromin, the protein encoded by the tumor suppressor gene, result in dysregulation of the RAS/MAPK pathway leading to uncontrolled cell growth and migration. Neurofibromin is highly expressed in several cell lineages including melanocytes, glial cells, neurons, and Schwann cells. Individuals with NF1 possess a genetic predisposition to central nervous system neoplasms, particularly gliomas affecting the visual pathway, known as optic pathway gliomas (OPGs). While OPGs are typically asymptomatic and benign, they can induce visual impairment in some patients. This review provides insight into the spectrum and visual outcomes of NF1, current diagnostic techniques and therapeutic interventions, and explores the influence of NF1-OPGS on visual abnormalities. We focus on recent advancements in preclinical animal models to elucidate the underlying mechanisms of NF1 pathology and therapies targeting NF1-OPGs. Overall, our review highlights the involvement of retinal ganglion cell dysfunction and degeneration in NF1 disease, and the need for further research to transform scientific laboratory discoveries to improved patient outcomes.
PubMed: 38804352
DOI: 10.3390/vision8020031 -
Cureus Jul 2023Multiple sclerosis is a neurological disorder categorized by inflammatory processes with a high prevalence worldwide. It affects both motor and sensory pathways and is... (Review)
Review
Multiple sclerosis is a neurological disorder categorized by inflammatory processes with a high prevalence worldwide. It affects both motor and sensory pathways and is also associated with the visual pathway. Fingolimod is a commonly used drug for relapsing-remitting multiple sclerosis. It is a sphingosine 1-phosphate modulator acting on its receptors for immune cell accumulation, neuronal function, embryological development, vascular permeability, smooth muscle cell function, and endothelial barrier maintenance. This review aims to understand the processes, mechanisms, risks, and management of fingolimod-associated macular edema. Due to the anti-inflammatory properties of fingolimod, it decreases various cytokines, including interleukin (IL)-1B and IL-6, spike wave, and spike amplitude, in electrophysiological activities and decreases insoluble receptors for advanced glycation end product ligand. A daily dosage of 0.5 mg of fingolimod has an increased association with macular edema. The serious adverse events of fingolimod are lymphopenia, cardiovascular events, ocular events, and carcinoma. Fingolimod decreases brain volume and increases vascular permeability, resulting in increased macular volume and damage to the blood-retinal barrier, which causes an increased risk for macular edema. Cystoid macular edema is more common in older individuals suffering from comorbidities affecting the retina, such as diabetes, or those undergoing ophthalmological surgeries. This review also highlights the importance of regular ophthalmology examinations on patients consuming fingolimod both in the initial stages and chronic use. The treatment options for macular edema include nonsteroidal anti-inflammatory drugs, acetazolamide, triamcinolone, ketorolac, corticosteroids, and intravitreal procedures.
PubMed: 37551255
DOI: 10.7759/cureus.41520 -
Neural Networks : the Official Journal... Aug 2023Motion perception is an essential ability for animals and artificially intelligent systems interacting effectively, safely with surrounding objects and environments.... (Review)
Review
Motion perception is an essential ability for animals and artificially intelligent systems interacting effectively, safely with surrounding objects and environments. Biological visual systems, that have naturally evolved over hundreds-million years, are quite efficient and robust for motion perception, whereas artificial vision systems are far from such capability. This paper argues that the gap can be significantly reduced by formulation of ON/OFF channels in motion perception models encoding luminance increment (ON) and decrement (OFF) responses within receptive field, separately. Such signal-bifurcating structure has been found in neural systems of many animal species articulating early motion is split and processed in segregated pathways. However, the corresponding biological substrates, and the necessity for artificial vision systems have never been elucidated together, leaving concerns on uniqueness and advantages of ON/OFF channels upon building dynamic vision systems to address real world challenges. This paper highlights the importance of ON/OFF channels in motion perception through surveying current progress covering both neuroscience and computationally modelling works with applications. Compared to related literature, this paper for the first time provides insights into implementation of different selectivity to directional motion of looming, translating, and small-sized target movement based on ON/OFF channels in keeping with soundness and robustness of biological principles. Existing challenges and future trends of such bio-plausible computational structure for visual perception in connection with hotspots of machine learning, advanced vision sensors like event-driven camera finally are discussed.
Topics: Animals; Motion Perception; Visual Perception; Vision, Ocular; Visual Pathways; Motion
PubMed: 37263088
DOI: 10.1016/j.neunet.2023.05.031 -
Current Neurology and Neuroscience... Mar 2024In this review, we will describe current methods for visual field testing in neuro-ophthalmic clinical practice and research, develop terminology that accurately... (Review)
Review
PURPOSE OF REVIEW
In this review, we will describe current methods for visual field testing in neuro-ophthalmic clinical practice and research, develop terminology that accurately describes patterns of field deficits, and discuss recent advances such as augmented or virtual reality-based perimetry and the use of artificial intelligence in visual field interpretation.
RECENT FINDINGS
New testing strategies that reduce testing times, improve patient comfort, and increase sensitivity for detecting small central or paracentral scotomas have been developed for static automated perimetry. Various forms of machine learning-based tools such as archetypal analysis are being tested to quantitatively depict and monitor visual field abnormalities in optic neuropathies. Studies show that the combined use of optical coherence tomography and standard automated perimetry to determine the structure-function relationship improves clinical care in neuro-ophthalmic disorders. Visual field assessment must be performed in all patients with neuro-ophthalmic disorders affecting the afferent visual pathway. Quantitative visual field analysis using standard automated perimetry is critical in initial diagnosis, monitoring disease progression, and guidance of therapeutic plans. Visual field defects can adversely impact activities of daily living such as reading, navigation, and driving and thus impact quality of life. Visual field testing can direct appropriate occupational low vision rehabilitation in affected individuals.
Topics: Humans; Visual Fields; Artificial Intelligence; Activities of Daily Living; Quality of Life; Optic Nerve Diseases; Visual Field Tests
PubMed: 38289405
DOI: 10.1007/s11910-024-01332-3 -
EMBO Reports Oct 2023The formation of social memory between individuals of the opposite sex is crucial for expanding mating options or establishing monogamous pair bonding. A specialized...
The formation of social memory between individuals of the opposite sex is crucial for expanding mating options or establishing monogamous pair bonding. A specialized neuronal circuit that regulates social memory could enhance an individual's mating opportunities and provide a parallel pathway for computing social behaviors. While the influence of light exposure on various forms of memory, such as fear and object memory, has been studied, its modulation of social recognition memory remains unclear. Here, we demonstrate that acute exposure to light impairs social recognition memory (SRM) in mice. Unlike sound and touch stimuli, light inhibits oxytocin neurons in the supraoptic nucleus (SON) via M1 SON-projecting intrinsically photosensitive retinal ganglion cells (ipRGCs) and GABAergic neurons in the perinuclear zone of the SON (pSON). We further show that optogenetic activation of SON oxytocin neurons using channelrhodopsin is sufficient to enhance SRM performance, even under light conditions. Our findings unveil a dedicated neuronal circuit through which luminance affects SRM, utilizing a non-image-forming visual pathway, distinct from the canonical modulatory role of the oxytocin system.
PubMed: 37531065
DOI: 10.15252/embr.202356839 -
Neuroscience Research Nov 2023The retinal neuronal circuit is the first stage of visual processing in the central nervous system. The efforts of scientists over the last few decades indicate that the... (Review)
Review
The retinal neuronal circuit is the first stage of visual processing in the central nervous system. The efforts of scientists over the last few decades indicate that the retina is not merely an array of photosensitive cells, but also a processor that performs various computations. Within a thickness of only ∼200 µm, the retina consists of diverse forms of neuronal circuits, each of which encodes different visual features. Since the discovery of direction-selective cells by Horace Barlow and Richard Hill, the mechanisms that generate direction selectivity in the retina have remained a fascinating research topic. This review provides an overview of recent advances in our understanding of direction-selectivity circuits. Beyond the conventional wisdom of direction selectivity, emerging findings indicate that the retina utilizes complicated and sophisticated mechanisms in which excitatory and inhibitory pathways are involved in the efficient encoding of motion information. As will become evident, the discovery of computational motifs in the retina facilitates an understanding of how sensory systems establish feature selectivity.
Topics: Retinal Ganglion Cells; Retina; Visual Perception; Central Nervous System; Visual Pathways; Motion Perception
PubMed: 37352934
DOI: 10.1016/j.neures.2023.06.003 -
Journal of Clinical Medicine Mar 2024Neuroplasticity is a complex process that is heightened during time-sensitive periods of pre- and postnatal brain development. It continues, albeit to a lesser extent,... (Review)
Review
Neuroplasticity is a complex process that is heightened during time-sensitive periods of pre- and postnatal brain development. It continues, albeit to a lesser extent, throughout adolescence and young adulthood. Congenital visual deprivation is well-known and explored in human-model behavioral research. In this study, we review existing research on neuroadaptations and neuroplasticity of the visual pathway as a result of inherited retinal diseases (IRD), focusing on data concerning congenital bilateral visual deprivation in humans published in PubMed in the past 5 years, including 18 articles. We highlight evidence about the anatomical and behavioral aspects of neuroplasticity as different brain responses to different types of visual deprivation. We also focus on various very interesting aspects of the cross-modal functional reorganization of the visual and auditory cortex as an example of brain plasticity due to combined visual and auditory loss. Our study shows that central nervous system magnetic resonance imaging (MRI) advancements have allowed researchers to report previously elusive anatomical evidence. Patients with a known mechanism of IRD-examined with high magnetic field MRI and functional MRI-have been proven to be adequate models to explore neuroadaptations of the visual pathway due to bilateral, early, and late visual deprivation.
PubMed: 38541998
DOI: 10.3390/jcm13061775 -
Frontiers in Neuroscience 2023
PubMed: 37795189
DOI: 10.3389/fnins.2023.1287762