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Acta Ophthalmologica Aug 2015Toxic optic neuropathy (TON) is caused by the damage to the optic nerve through different toxins, including drugs, metals, organic solvents, methanol and carbon dioxide.... (Review)
Review
Toxic optic neuropathy (TON) is caused by the damage to the optic nerve through different toxins, including drugs, metals, organic solvents, methanol and carbon dioxide. A similar clinical picture may also be caused by nutritional deficits, including B vitamins, folic acid and proteins with sulphur-containing amino acids. This review summarizes the present knowledge on disease-causing factors, clinical presentation, diagnostics and treatment in TON. It discusses in detail known and hypothesized relations between drugs, including tuberculostatic drugs, antimicrobial agents, antiepileptic drugs, antiarrhythmic drugs, disulfiram, halogenated hydroquinolones, antimetabolites, tamoxifen and phosphodiesterase type 5 inhibitors and optic neuropathy.
Topics: Drug-Related Side Effects and Adverse Reactions; Humans; Optic Nerve; Optic Nerve Diseases; Pharmaceutical Preparations
PubMed: 25159832
DOI: 10.1111/aos.12515 -
Current Opinion in Neurology Feb 2021Negative findings on neuroimaging are part of the diagnostic criteria for idiopathic intracranial hypertension (IIH), a syndrome characterized by increased intracranial... (Review)
Review
PURPOSE OF REVIEW
Negative findings on neuroimaging are part of the diagnostic criteria for idiopathic intracranial hypertension (IIH), a syndrome characterized by increased intracranial pressure (ICP). Some positive neuroimaging findings are associated with increased ICP, but their role in diagnosis of IIH has not been established. We provide an overview of these findings and their relevance for diagnosis of raised intracranial pressure.
RECENT FINDINGS
MRI acquisition techniques have significantly improved in the last few decades leading to better characterization of the intracranial changes associated with IIH, including empty sella turcica, optic nerve tortuosity, distension of the optic nerve sheath, posterior globe flattening, slit-like ventricles, and venous sinus stenosis. These may be MRI biomarkers of increased ICP. Prevalence difference between people with and without increased ICP, and reversibility of these MRI findings following treatment of increased ICP inform evaluation of their diagnostic potential.
SUMMARY
MRI and magnetic resonance venography findings are important tools in the diagnosis of IIH. Empty sella turcica, optic nerve protrusion, distension of the optic nerve sheath, optic nerve tortuosity, posterior globe flattening, and transverse sinus stenosis have been found to be the most promising diagnostic markers for IIH, although absence of these findings does not rule out the diagnosis.
Topics: Biomarkers; Constriction, Pathologic; Humans; Intracranial Hypertension; Magnetic Resonance Imaging; Neuroimaging; Optic Nerve; Pseudotumor Cerebri
PubMed: 33230036
DOI: 10.1097/WCO.0000000000000885 -
Proceedings of the National Academy of... Aug 2023Although the visual system extends through the brain, most vision loss originates from defects in the eye. Its central element is the neural retina, which senses light,...
Although the visual system extends through the brain, most vision loss originates from defects in the eye. Its central element is the neural retina, which senses light, processes visual signals, and transmits them to the rest of the brain through the optic nerve (ON). Surrounding the retina are numerous other structures, conventionally divided into anterior and posterior segments. Here, we used high-throughput single-nucleus RNA sequencing (snRNA-seq) to classify and characterize cells in six extraretinal components of the posterior segment: ON, optic nerve head (ONH), peripheral sclera, peripapillary sclera (PPS), choroid, and retinal pigment epithelium (RPE). Defects in each of these tissues are associated with blinding diseases-for example, glaucoma (ONH and PPS), optic neuritis (ON), retinitis pigmentosa (RPE), and age-related macular degeneration (RPE and choroid). From ~151,000 single nuclei, we identified 37 transcriptomically distinct cell types, including multiple types of astrocytes, oligodendrocytes, fibroblasts, and vascular endothelial cells. Our analyses revealed a differential distribution of many cell types among distinct structures. Together with our previous analyses of the anterior segment and retina, the data presented here complete a "Version 1" cell atlas of the human eye. We used this atlas to map the expression of >180 genes associated with the risk of developing glaucoma, which is known to involve ocular tissues in both anterior and posterior segments as well as the neural retina. Similar methods can be used to investigate numerous additional ocular diseases, many of which are currently untreatable.
Topics: Humans; Transcriptome; Endothelial Cells; Optic Disk; Glaucoma; Optic Nerve; Sclera
PubMed: 37566633
DOI: 10.1073/pnas.2306153120 -
AJNR. American Journal of Neuroradiology Jul 2019
Topics: Humans; Neuroimaging; Optic Disk; Optic Nerve; Pseudotumor Cerebri
PubMed: 31171516
DOI: 10.3174/ajnr.A6094 -
Progress in Retinal and Eye Research Mar 2021Glial cells are critically important for maintenance of neuronal activity in the central nervous system (CNS), including the optic nerve (ON). However, the ON has... (Review)
Review
Glial cells are critically important for maintenance of neuronal activity in the central nervous system (CNS), including the optic nerve (ON). However, the ON has several unique characteristics, such as an extremely high myelination level of retinal ganglion cell (RGC) axons throughout the length of the nerve (with virtually all fibers myelinated by 7 months of age in humans), lack of synapses and very narrow geometry. Moreover, the optic nerve head (ONH) - a region where the RGC axons exit the eye - represents an interesting area that is morphologically distinct in different species. In many cases of multiple sclerosis (demyelinating disease of the CNS) vision problems are the first manifestation of the disease, suggesting that RGCs and/or glia in the ON are more sensitive to pathological conditions than cells in other parts of the CNS. Here, we summarize current knowledge on glial organization and function in the ON, focusing on glial support of RGCs. We cover both well-established concepts on the important role of glial cells in ON health and new findings, including novel insights into mechanisms of remyelination, microglia/NG2 cell-cell interaction, astrocyte reactivity and the regulation of reactive astrogliosis by mitochondrial fragmentation in microglia.
Topics: Animals; Axons; Humans; Neuroglia; Optic Nerve; Retinal Ganglion Cells
PubMed: 32771538
DOI: 10.1016/j.preteyeres.2020.100886 -
Ophthalmology Feb 2021The spaceflight-associated neuro-ocular syndrome (SANS) affects astronauts on missions to the International Space Station (ISS). The SANS has blurred vision and ocular...
PURPOSE
The spaceflight-associated neuro-ocular syndrome (SANS) affects astronauts on missions to the International Space Station (ISS). The SANS has blurred vision and ocular changes as typical features. The objective of this study was to investigate if microgravity can create deformations or movements of the eye or optic nerve, and if such changes could be linked to SANS.
DESIGN
Cohort study.
PARTICIPANTS
Twenty-two astronauts (age 48 ± 4 years).
METHODS
The intervention consisted of time in microgravity at the ISS. We co-registered pre- and postspaceflight magnetic resonance imaging (MRI) scans and generated centerline representations of the optic nerve. The coordinates for the optic nerve head (ONH) and optic chiasm (OC) ends of the optic nerve were recorded along with the entire centerline path.
MAIN OUTCOME MEASURES
Optic nerve length, ONH movement, and OC movement after time in microgravity.
RESULTS
Optic nerve length increased (0.80 ± 0.74 mm, P < 0.001), primarily reflecting forward ONH displacement (0.63 ± 0.53 mm, P < 0.001). The forward displacement was positively related to mission duration, preflight body weight, and clinical manifestations of SANS. We also detected upward displacement of the OC (0.39 ± 0.50 mm, P = 0.002), indicative of brain movement, but this observation could not be linked to SANS.
CONCLUSIONS
The spaceflight-induced optic nerve lengthening and anterior movement of the ONH support that SANS is caused by an altered pressure difference between the brain and the eye, leading to a forward push on the posterior of the eye. Body weight is a potential contributing risk factor. Direct assessment of intracranial pressure in space is required to verify the implicated mechanism behind the ocular findings in SANS.
Topics: Astronauts; Cohort Studies; Extraterrestrial Environment; Female; Humans; Intracranial Pressure; Magnetic Resonance Imaging; Male; Middle Aged; Optic Disk; Optic Nerve; Papilledema; Space Flight; Syndrome; Time Factors; Vision Disorders; Weightlessness
PubMed: 32659310
DOI: 10.1016/j.ophtha.2020.07.007 -
Restorative Neurology and Neuroscience 2019The optic nerve conveys information about the outside world from the retina to multiple subcortical relay centers. Until recently, the optic nerve was widely believed to... (Review)
Review
The optic nerve conveys information about the outside world from the retina to multiple subcortical relay centers. Until recently, the optic nerve was widely believed to be incapable of re-growing if injured, with dire consequences for victims of traumatic, ischemic, or neurodegenerative diseases of this pathway. Over the past 10-20 years, research from our lab and others has made considerable progress in defining factors that normally suppress axon regeneration and the ability of retinal ganglion cells, the projection neurons of the retina, to survive after nerve injury. Here we describe research from our lab on the role of inflammation-derived growth factors, suppression of inter-cellular signals among diverse retinal cell types, and combinatorial therapies, along with related studies from other labs, that enable animals with optic nerve injury to regenerate damaged retinal axons back to the brain. These studies raise the possibility that vision might one day be restored to people with optic nerve damage.
Topics: Animals; Axons; Humans; Inflammation Mediators; Nerve Regeneration; Optic Nerve; Optic Nerve Injuries; Retinal Ganglion Cells
PubMed: 31609715
DOI: 10.3233/RNN-190960 -
Archives of Toxicology Feb 2022Methanol-induced optic neuropathy (Me-ION) is a serious condition that may result in long-term or irreversible visual impairment or even blindness secondary to damage... (Review)
Review
Methanol-induced optic neuropathy (Me-ION) is a serious condition that may result in long-term or irreversible visual impairment or even blindness secondary to damage and loss of function of the optic nerve and retina. Me-ION shows a tendency to occur as mass poisonings around the world with a clear predilection for poor societies in developing countries. The main mechanism underlying the molecular basis of Me-ION is the inhibition of the mitochondrial oxidative phosphorylation process through the binding of the toxic metabolite of methanol-formic acid-with the key enzyme of this process-cytochrome c oxidase. However, other mechanisms, including damage to the eye tissues by oxidative stress causing the intensification of the oxidative peroxidation process with the formation of cytotoxic compounds, as well as an increase in the synthesis of pro-inflammatory cytokines and influence on the expression of key proteins responsible for maintaining cell homeostasis, also play an important role in the pathogenesis of Me-ION. Histopathological changes in the eye tissues are mainly manifested as the degeneration of axons and glial cells of the optic nerve, often with accompanying damage of the retina that may involve all its layers. Despite the development of therapeutic approaches, persistent visual sequelae are seen in 30-40% of survivors. Thus, Me-ION continues to be an important problem for healthcare systems worldwide.
Topics: Animals; Axons; Formates; Humans; Methanol; Mitochondria; Optic Nerve; Optic Nerve Diseases; Oxidative Stress; Retina
PubMed: 34988610
DOI: 10.1007/s00204-021-03202-0 -
Archives of Pathology & Laboratory... Jan 2017Ischemic optic neuropathy (ION) describes a state of hypoxic injury of the optic nerve. Clinically, ION is divided into anterior and posterior forms defined by the... (Review)
Review
Ischemic optic neuropathy (ION) describes a state of hypoxic injury of the optic nerve. Clinically, ION is divided into anterior and posterior forms defined by the presence or absence of optic disc swelling, respectively. It is further classified as arteritic when secondary to vasculitis, and nonarteritic when not. The site of vascular occlusion for anterior ION from giant cell arteritis is the short posterior ciliary arteries, but mechanical vascular obstruction does not play a role in most nonarteritic cases. Histologically, ION is characterized by axon and glial necrosis, edema, and a sparse mononuclear response. Like other ischemic injuries, the morphologic alternations in the nerve are time dependent. A variant of ION called cavernous degeneration (of Schnabel) features large cystic spaces filled with mucin. Several conditions can histologically mimic cavernous degeneration of the optic nerve. The scarcity of cases of ION examined histologically has contributed to an incomplete understanding of its pathogenesis.
Topics: Arteritis; Diagnosis, Differential; Humans; Optic Disk; Optic Nerve; Optic Neuropathy, Ischemic
PubMed: 28029908
DOI: 10.5858/arpa.2016-0027-RS -
International Journal of Molecular... Jan 2023Common risk factors for many ocular pathologies involve non-pathologic, age-related damage to the optic nerve. Understanding the mechanisms of age-related changes can... (Review)
Review
Common risk factors for many ocular pathologies involve non-pathologic, age-related damage to the optic nerve. Understanding the mechanisms of age-related changes can facilitate targeted treatments for ocular pathologies that arise at any point in life. In this review, we examine these age-related, neurodegenerative changes in the optic nerve, contextualize these changes from the anatomic to the molecular level, and appreciate their relationship with ocular pathophysiology. From simple structural and mechanical changes at the optic nerve head (ONH), to epigenetic and biochemical alterations of tissue and the environment, multiple age-dependent mechanisms drive extracellular matrix (ECM) remodeling, retinal ganglion cell (RGC) loss, and lowered regenerative ability of respective axons. In conjunction, aging decreases the ability of myelin to preserve maximal conductivity, even with "successfully" regenerated axons. Glial cells, however, regeneratively overcompensate and result in a microenvironment that promotes RGC axonal death. Better elucidating optic nerve neurodegeneration remains of interest, specifically investigating human ECM, RGCs, axons, oligodendrocytes, and astrocytes; clarifying the exact processes of aged ocular connective tissue alterations and their ultrastructural impacts; and developing novel technologies and pharmacotherapies that target known genetic, biochemical, matrisome, and neuroinflammatory markers. Management models should account for age-related changes when addressing glaucoma, diabetic retinopathy, and other blinding diseases.
Topics: Animals; Humans; Aged; Optic Nerve; Optic Disk; Glaucoma; Retinal Ganglion Cells; Axons; Aging; Disease Models, Animal
PubMed: 36768896
DOI: 10.3390/ijms24032573