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Annual Review of Vision Science Sep 2020Binocular vision depends on retinal ganglion cell (RGC) axon projection either to the same side or to the opposite side of the brain. In this article, we review the... (Review)
Review
Binocular vision depends on retinal ganglion cell (RGC) axon projection either to the same side or to the opposite side of the brain. In this article, we review the molecular mechanisms for decussation of RGC axons, with a focus on axon guidance signaling at the optic chiasm and ipsi- and contralateral axon organization in the optic tract prior to and during targeting. The spatial and temporal features of RGC neurogenesis that give rise to ipsilateral and contralateral identity are described. The albino visual system is highlighted as an apt comparative model for understanding RGC decussation, as albinos have a reduced ipsilateral projection and altered RGC neurogenesis associated with perturbed melanogenesis in the retinal pigment epithelium. Understanding the steps for RGC specification into ipsi- and contralateral subtypes will facilitate differentiation of stem cells into RGCs with proper navigational abilities for effective axon regeneration and correct targeting of higher-order visual centers.
Topics: Animals; Axons; Mice; Nerve Regeneration; Optic Chiasm; Retinal Ganglion Cells; Vision, Binocular; Visual Pathways
PubMed: 32396770
DOI: 10.1146/annurev-vision-091517-034306 -
Frontiers in Neuroscience 2023Glaucoma is the first major category of irreversible blinding eye illnesses worldwide. Its leading cause is the death of retinal ganglion cells and their axons, which... (Review)
Review
Glaucoma is the first major category of irreversible blinding eye illnesses worldwide. Its leading cause is the death of retinal ganglion cells and their axons, which results in the loss of vision. Research indicates that glaucoma affects the optic nerve and the whole visual pathway. It also reveals that degenerative lesions caused by glaucoma can be found outside the visual pathway. Diffusion tensor imaging (DTI) is a magnetic resonance imaging (MRI) technique that can investigate the complete visual system, including alterations in the optic nerve, optic chiasm, optic tract, lateral geniculate nuclear, and optic radiation. In order to provide a more solid foundation for the degenerative characteristics of glaucoma, this paper will discuss the standard diagnostic techniques for glaucoma through a review of the literature, describe the use of DTI technology in glaucoma in humans and animal models, and introduce these techniques. With the advancement of DTI technology and its coupling with artificial intelligence, DTI represents a potential future for MRI technology in glaucoma research.
PubMed: 36816120
DOI: 10.3389/fnins.2023.1125638 -
Nature Communications Jul 2022The inability of neurons to regenerate long axons within the CNS is a major impediment to improving outcome after spinal cord injury, stroke, and other CNS insults....
The inability of neurons to regenerate long axons within the CNS is a major impediment to improving outcome after spinal cord injury, stroke, and other CNS insults. Recent advances have uncovered an intrinsic program that involves coordinate regulation by multiple transcription factors that can be manipulated to enhance growth in the peripheral nervous system. Here, we use a systems genomics approach to characterize regulatory relationships of regeneration-associated transcription factors, identifying RE1-Silencing Transcription Factor (REST; Neuron-Restrictive Silencer Factor, NRSF) as a predicted upstream suppressor of a pro-regenerative gene program associated with axon regeneration in the CNS. We validate our predictions using multiple paradigms, showing that mature mice bearing cell type-specific deletions of REST or expressing dominant-negative mutant REST show improved regeneration of the corticospinal tract and optic nerve after spinal cord injury and optic nerve crush, which is accompanied by upregulation of regeneration-associated genes in cortical motor neurons and retinal ganglion cells, respectively. These analyses identify a role for REST as an upstream suppressor of the intrinsic regenerative program in the CNS and demonstrate the utility of a systems biology approach involving integrative genomics and bio-informatics to prioritize hypotheses relevant to CNS repair.
Topics: Animals; Axons; Mice; Nerve Regeneration; Repressor Proteins; Retinal Ganglion Cells; Spinal Cord Injuries; Transcription Factors
PubMed: 35906210
DOI: 10.1038/s41467-022-31960-7 -
Journal of Comparative Pathology Feb 2023We describe gross and histopathological features of multiple ocular and neuro-ophthalmic abnormalities in a fox squirrel (Sciurus niger). Ophthalmic findings included...
We describe gross and histopathological features of multiple ocular and neuro-ophthalmic abnormalities in a fox squirrel (Sciurus niger). Ophthalmic findings included severe bilateral microphthalmos, with the right eye more affected than the left. Histopathology confirmed severe microphthalmia, aphakia, disorganized retinal tissue and small optic nerves, as well as agenesis of the optic chiasm and optic tract. This combination of neuro-ophthalmic abnormalities has not been previously described in wild animals.
Topics: Animals; Microphthalmos; Optic Chiasm; Sciuridae; Retina; Aphakia; Rodent Diseases
PubMed: 36791601
DOI: 10.1016/j.jcpa.2023.01.001 -
CNS Drugs Apr 2023Satralizumab (Enspryng) is a monoclonal antibody that blocks the interleukin-6 (IL-6) receptor and is approved for the treatment of neuromyelitis optica spectrum... (Review)
Review
Satralizumab (Enspryng) is a monoclonal antibody that blocks the interleukin-6 (IL-6) receptor and is approved for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in patients who are aquaporin-4 immunoglobulin G (AQP4-IgG) seropositive. Patients with NMOSD are at risk of recurrent autoimmune attacks that primarily target the optic nerves and spinal cord but may also target other regions of the central nervous system; these attacks can lead to life-long disability. In the randomized, placebo-controlled phase III SAkuraSky and SAkuraStar trials, subcutaneous satralizumab as an add-on to immunosuppressive therapy or as a monotherapy, respectively, significantly reduced the risk of relapse compared with placebo in patients who were AQP4-IgG seropositive with NMOSD. Satralizumab was well tolerated; the most common adverse events were infection, headache, arthralgia, decreased white blood cell count, hyperlipidaemia and injection-related reactions. In the EU, satralizumab is the first IL-6 receptor blocker to be approved for treatment of AQP4-IgG-seropositive patients with NMOSD, has the potential advantage of subcutaneous administration, and is the only targeted treatment approved for adolescent patients with this disorder. Thus, satralizumab is a valuable treatment option for patients with NMOSD.
Topics: Adolescent; Humans; Neuromyelitis Optica; Autoantibodies; Antibodies, Monoclonal, Humanized; Aquaporin 4; Immunoglobulin G
PubMed: 36933107
DOI: 10.1007/s40263-023-00995-9 -
Neuroscience and Biobehavioral Reviews Sep 2020We conducted the first meta-analysis of whole-brain voxel-based DTI studies in childhood maltreatment to elucidate regions of white matter (WM) microstructure... (Meta-Analysis)
Meta-Analysis Review
We conducted the first meta-analysis of whole-brain voxel-based DTI studies in childhood maltreatment to elucidate regions of white matter (WM) microstructure abnormality relative to non-maltreated controls. Fourteen DTI datasets were included, comprising 386 individuals with childhood maltreatment and 612 non-maltreated controls. Anisotropic effect-size signed differential mapping, a voxel-based meta-analytic method, was used to examine regions of altered fractional anisotropy (FA) in maltreated individuals relative to controls. Maltreated individuals had significantly reduced FA in the left anterior thalamic radiation and bilateral fornix, optic radiations, inferior longitudinal fasciculus, and inferior frontal-occipital fasciculus, along with the anterior portions of the corpus callosum. There were no regions with increased FA. Decreased FA in the callosal genu and body remained in subgroup analyses of unmedicated and drug-free participants. Findings suggest that childhood maltreatment is associated with widespread WM microstructural abnormalities particularly evident in the fornix, corpus callosum and optic radiations, where the neural pathways linking fronto-limbic and occipital visual cortices presumably involved in conveying and processing the (aversive) experience may be compromised in this population.
Topics: Anisotropy; Brain; Diffusion Tensor Imaging; Humans; Neural Pathways; White Matter
PubMed: 32659288
DOI: 10.1016/j.neubiorev.2020.07.004 -
Neuron Aug 2020At various stages of the visual system, visual responses are modulated by arousal. Here, we find that in mice this modulation operates as early as in the first synapse...
At various stages of the visual system, visual responses are modulated by arousal. Here, we find that in mice this modulation operates as early as in the first synapse from the retina and even in retinal axons. To measure retinal activity in the awake, intact brain, we imaged the synaptic boutons of retinal axons in the superior colliculus. Their activity depended not only on vision but also on running speed and pupil size, regardless of retinal illumination. Arousal typically reduced their visual responses and selectivity for direction and orientation. Recordings from retinal axons in the optic tract revealed that arousal modulates the firing of some retinal ganglion cells. Arousal had similar effects postsynaptically in colliculus neurons, independent of activity in the other main source of visual inputs to the colliculus, the primary visual cortex. These results indicate that arousal modulates activity at every stage of the mouse visual system.
Topics: Animals; Arousal; Axons; Locomotion; Mice; Neurons; Optic Tract; Orientation, Spatial; Presynaptic Terminals; Retinal Ganglion Cells; Superior Colliculi; Visual Pathways; Wakefulness
PubMed: 32445624
DOI: 10.1016/j.neuron.2020.04.026 -
World Neurosurgery Jun 2020To comprehensively compare the vision improvement rate in patients with traumatic optic neuropathy with different surgical timing and other different preoperative... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To comprehensively compare the vision improvement rate in patients with traumatic optic neuropathy with different surgical timing and other different preoperative conditions.
METHODS
PubMed, Embase, and MEDLINE Ovid were searched to identify studies. We performed subgroup analyses for differences in the surgical timing, surgical approach, optic canal fractures, state of consciousness after trauma, time of visual loss development, incision of the optic nerve sheath, and treatment methods.
RESULTS
A total of 74 studies involving 6084 patients were included in the final analysis. In the groups of patients with early (≤3 days), middle (4-7 days), and late (>7 days) surgical interventions, 58.4%, 53.2%, and 45.4% demonstrated visual improvements, respectively. The results of the statistical analysis revealed that patients with early surgical intervention had a higher improvement rate than patients with late surgical intervention (P = 0.00953). The improvement rate was significantly lower for patients who presented with no light perception before surgery than for patients whose vision was better than no light perception (relative risk, 0.498; 95% confidence interval [CI], 0.443-0.561; P = 0.001) and lower for patients with immediate visual loss after trauma than for those with secondary visual loss (relative risk, 0.639; 95% CI, 0.498-0.819; P = 0.001).
CONCLUSIONS
We recommend that patients seek medical treatment as soon as possible after traumatic optic nerve injury, and patients with secondary injuries can have a good recovery effect while still living with light perception or more. The option of treatment and whether to incise the optic nerve sheath still remains controversial.
Topics: Decompression, Surgical; Humans; Ophthalmologic Surgical Procedures; Optic Nerve Injuries; Optic Tract; Patient Selection; Prognosis; Time-to-Treatment; Treatment Outcome; Vision Disorders; Visual Acuity
PubMed: 32169622
DOI: 10.1016/j.wneu.2020.03.007 -
Frontiers in Immunology 2022While the respiratory tract is the primary route of entry for SARS-CoV-2, evidence shows that the virus also impacts the central nervous system. Intriguingly, case... (Review)
Review
While the respiratory tract is the primary route of entry for SARS-CoV-2, evidence shows that the virus also impacts the central nervous system. Intriguingly, case reports have documented SARS-CoV-2 patients presenting with demyelinating lesions in the brain, spinal cord, and optic nerve, suggesting possible implications in neuroimmune disorders such as multiple sclerosis (MS) and other related neuroimmune disorders. However, the cellular mechanisms underpinning these observations remain poorly defined. The goal of this paper was to review the literature to date regarding possible links between SARS-CoV-2 infection and neuroimmune demyelinating diseases such as MS and its related disorders, with the aim of positing a hypothesis for disease exacerbation. The literature suggests that SARS-CoV, SARS-CoV-2, and orthologous murine coronaviruses invade the CNS the olfactory bulb, spreading to connected structures retrograde transport. We hypothesize that a glial inflammatory response may contribute to damaged oligodendrocytes and blood brain barrier (BBB) breakdown, allowing a second route for CNS invasion and lymphocyte infiltration. Potential for molecular mimicry and the stimulation of autoreactive T cells against myelin is also described. It is imperative that further studies on SARS-CoV-2 neuroinvasion address the adverse effects of the virus on myelin and exacerbation of MS symptoms, as nearly 3 million people suffer from MS worldwide.
Topics: Animals; COVID-19; Central Nervous System; Disease Progression; Humans; Mice; Multiple Sclerosis; SARS-CoV-2
PubMed: 35572514
DOI: 10.3389/fimmu.2022.871276 -
Journal of Clinical Medicine Jul 2023Granulomatosis with polyangiitis (GPA), formerly referred to as Wegener's disease, is a form of ANCA-associated vasculitis. It manifests mainly in the kidneys and the...
Granulomatosis with polyangiitis (GPA), formerly referred to as Wegener's disease, is a form of ANCA-associated vasculitis. It manifests mainly in the kidneys and the upper respiratory tract, but ocular involvement is not uncommon. In this article, four cases with ocular manifestations are presented with comprehensive photographic documentation. We describe the way to proper diagnosis, which may be long, the possible treatment, and the final outcomes. Our patients had the following ocular manifestations of GPA: retinal vasculitis, anterior necrotizing scleritis, medial orbital wall and orbital floor erosion with middle face deformation, compressive optic neuropathy due to retrobulbar inflammatory mass, and the abscess of the eyelids, inflammatory intraorbital mass causing exophthalmos and diplopia. This manuscript includes the description of severe forms of GPA, the initial signs and symptoms, relapses, and difficulties in achieving remission. The extraocular involvement is described with diagnostic modalities and laboratory findings. One of the reported cases was diagnosed by an ophthalmologist on the basis of ocular symptoms in the early stages of the disease. Our outcomes are compared with those discussed in the literature.
PubMed: 37445483
DOI: 10.3390/jcm12134448