scholarly journals An Experimental Model of Neuromyelitis Optica Spectrum Disorder–Optic Neuritis: Insights Into Disease Mechanisms

2021 ◽  
Vol 12 ◽  
Author(s):  
Sofie Forsberg Soerensen ◽  
Martin Wirenfeldt ◽  
Agnieszka Wlodarczyk ◽  
Marlene Thorsen Moerch ◽  
Reza Khorooshi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Optic Nerve ◽  
Optic Neuritis ◽  
Experimental Model ◽  
Neuromyelitis Optica ◽  
Intrathecal Injection ◽  
Aquaporin 4 ◽  
Type I ◽  
Optic Nerves ◽  
Disease Mechanisms

Background: Optic neuritis (ON) is a common inflammatory optic neuropathy, which often occurs in neuromyelitis optica spectrum disease (NMOSD). An experimental model of NMOSD-ON may provide insight into disease mechanisms.Objective: To examine the pathogenicity of autoantibodies targeting the astrocyte water channel aquaporin-4 [aquaporin-4 (AQP4)-immunoglobulin G (AQP4-IgG)] in the optic nerve.Materials and Methods: Purified IgG from an AQP4-IgG-positive NMOSD-ON patient was together with human complement (C) given to wild-type (WT) and type I interferon (IFN) receptor-deficient mice (IFNAR1-KO) as two consecutive intrathecal injections into cerebrospinal fluid via cisterna magna. The optic nerves were isolated, embedded in paraffin, cut for histological examination, and scored semi-quantitatively in a blinded fashion. In addition, optic nerves were processed to determine selected gene expression by quantitative real-time PCR.Results: Intrathecal injection of AQP4-IgG+C induced astrocyte pathology in the optic nerve with loss of staining for AQP4 and glial fibrillary acidic protein (GFAP), deposition of C, and demyelination, as well as upregulation of gene expression for interferon regulatory factor-7 (IRF7) and CXCL10. Such pathology was not seen in IFNAR1-KO mice nor in control mice.Conclusion: We describe induction of ON in an animal model for NMOSD and show a requirement for type I IFN signaling in the disease process.

scholarly journals The expanded spectrum of neuromyelitis optica: evidences for a new definition

2012 ◽  
Vol 70 (10) ◽  
pp. 807-813 ◽  
Author(s):  
Marco A Lana-Peixoto ◽  
Dagoberto Callegaro
Keyword(s):  
Optic Nerve ◽  
Optic Neuritis ◽  
Neuromyelitis Optica ◽  
Brain Mri ◽  
Transverse Myelitis ◽  
Aquaporin 4 ◽  
Longitudinally Extensive Transverse Myelitis ◽  
Index Event ◽  
Aquaporin 4 Antibody ◽  
Extensive Transverse Myelitis

Neuromyelitis optica (NMO) has been traditionally described as the association of recurrent or bilateral optic neuritis and longitudinally extensive transverse myelitis (LETM). Identification of aquaporin-4 antibody (AQP4-IgG) has deeply changed the concept of NMO. A spectrum of NMO disorders (NMOSD) has been formulated comprising conditions which include both AQP4-IgG seropositivity and one of the index events of the disease (recurrent or bilateral optic neuritis and LETM). Most NMO patients harbor asymptomatic brain MRI lesions, some of them considered as typical of NMO. Some patients with aquaporin-4 autoimmunity present brainstem, hypothalamic or encephalopathy symptoms either preceding an index event or occurring isolatedly with no evidence of optic nerve or spinal involvement. On the opposite way, other patients have optic neuritis or LETM in association with typical lesions of NMO on brain MRI and yet are AQP4-IgG seronegative. An expanded spectrum of NMO disorders is proposed to include these cases.

scholarly journals Deletion of arginase 2 attenuates neuroinflammation in an experimental model of optic neuritis

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0247901
Author(s):  
Amritha A. Candadai ◽  
Fang Liu ◽  
Abdelrahman Y. Fouda ◽  
Moaddey Alfarhan ◽  
Chithra D. Palani ◽  
...  
Keyword(s):  
Optic Neuritis ◽  
Experimental Model ◽  
Axonal Degeneration ◽  
Wild Type ◽  
Autoimmune Encephalomyelitis ◽  
Optic Nerves ◽  
Clinical Presentations ◽  
Retinal Neurodegeneration ◽  
The Impact ◽  
Experimental Autoimmune

Vision impairment due to optic neuritis (ON) is one of the major clinical presentations in Multiple Sclerosis (MS) and is characterized by inflammation and degeneration of the optic nerve and retina. Currently available treatments are only partially effective and have a limited impact on the neuroinflammatory pathology of the disease. A recent study from our laboratory highlighted the beneficial effect of arginase 2 (A2) deletion in suppressing retinal neurodegeneration and inflammation in an experimental model of MS. Utilizing the same model, the present study investigated the impact of A2 deficiency on MS-induced optic neuritis. Experimental autoimmune encephalomyelitis (EAE) was induced in wild-type (WT) and A2 knockout (A2-/-) mice. EAE-induced cellular infiltration, as well as activation of microglia and macrophages, were reduced in A2-/- optic nerves. Axonal degeneration and demyelination seen in EAE optic nerves were observed to be reduced with A2 deletion. Further, the lack of A2 significantly ameliorated astrogliosis induced by EAE. In conclusion, our findings demonstrate a critical involvement of arginase 2 in mediating neuroinflammation in optic neuritis and suggest the potential of A2 blockade as a targeted therapy for MS-induced optic neuritis.

scholarly journals Shear wave elastography in optic neuritis: diagnostic accuracy of the optic nerve and adjacent fat tissue values

2021 ◽  
Vol 21 (86) ◽  
pp. e194-e199
Author(s):  
Mustafa Devran Aybar ◽  
◽  
Onder Turna ◽  
Keyword(s):  
Optic Nerve ◽  
Diagnostic Accuracy ◽  
Optic Neuritis ◽  
Shear Wave ◽  
Shear Wave Elastography ◽  
Curve Analysis ◽  
Fat Tissue ◽  
Roc Curve Analysis ◽  
Optic Nerves ◽  
The Mean

Introduction: In this study, we attempt to determine the diagnostic performance of shear wave elastography of the optic nerve and adjacent fat tissue in patients with optic neuritis. Methods: The study included a patient group consisting of 72 eyes of 36 patients who were diagnosed with unilateral optic neuritis, and an age-matched control group of 36 eyes of 18 healthy subjects. The patient group consisted of 25 multiple sclerosis patients and 11 recurrent isolated optic neuritis patients. The mean shear wave elastography values of the optic nerves and intraorbital fat tissue adjacent optic nerves were recorded using m/s and kPa as units. ROC curve analysis was performed, and the diagnostic accuracy of shear wave elastography values was determined. Results: The mean shear wave elastography values of the optic nerves with neuritis (2.49 ± 0.41 m/s and 17.56 ± 4.42 kPa) were significantly higher than the values of the contralateral normal optic nerves (1.71 ± 0.32 m/s and 9.02 ± 2.34 kPa) (p = 0.006 and p = 0.004, respectively) in the optic neuritis group. The mean shear wave elastography values of intraorbital fat tissue adjacent optic nerves with neuritis (1.87 ± 0.32 m/s and 9.65 ± 1.12 kPa) were significantly higher than the values of the contralateral normal side (1.47 ± 0.27 m/s and 6.78 ± 1.14 kPa) (p = 0.025 and p = 0.022, respectively) in the optic neuritis group. ROC curve analysis showed a high diagnostic accuracy for determining optic neuritis with shear wave elastography values of the optic nerves (AUC 0.955 [95% CI, 0.933–0.978] in m/s and AUC 0.967 [95% CI, 0.940–0.985] in kPa). Conclusions: Shear wave elastography may be an important alternative diagnostic tool in the diagnosis of optic neuritis.

Features of anti-aquaporin 4 antibody-seropositive Chinese patients with neuromyelitis optica spectrum optic neuritis

2015 ◽  
Vol 262 (10) ◽  
pp. 2293-2304 ◽  
Author(s):  
Hongyang Li ◽  
Yanling Wang ◽  
Quangang Xu ◽  
Aidi Zhang ◽  
Huanfen Zhou ◽  
...  
Keyword(s):  
Optic Neuritis ◽  
Neuromyelitis Optica ◽  
Aquaporin 4 ◽  
Chinese Patients ◽  
Aquaporin 4 Antibody

On the Protective Effect of Lycium Barbarum Polysaccharide (LBP) on Optic Nerve Tissue and Retinal Ganglion Cells

2020 ◽  
Vol 10 (4) ◽  
pp. 443-448
Author(s):  
Shuzhen Wang ◽  
Zelin Xu ◽  
Yuanyuan Zhao ◽  
Chao Liu
Keyword(s):  
Optic Nerve ◽  
Optic Neuritis ◽  
Protective Effect ◽  
Intrathecal Injection ◽  
Nerve Damage ◽  
Nerve Tissue ◽  
Blue Staining ◽  
Lycium Barbarum ◽  
Optic Nerve Damage ◽  
Lycium Barbarum Polysaccharide

Background: The present paper established a model of optic neuritis injury by intrathecal injection of lipopolysaccharide (LPS) into the optic nerve, then explored the protective effect of Lycium Barbarum Polysaccharide (LBP) on optic nerve tissue and RGCs after injury. Material and methods: LPS was microinjected into the optic nerve of SD rats to induce optic neuritis. The histopathological variations of HE staining were observed in each group. The expressions of ED1/CD68 and GFAP were determined by immunofluorescence. The optic nerve repairment was evaluated by lux solid blue staining. TUNEL detects retinal cell apoptosis. Western blot was used to detect differences in expressions of related proteins. Results: LBP can alleviate the degree of optic nerve damage in rats with optic neuritis injury, inhibit the increase of LPS-induced macrophages and astrocytes in the optic nerve and retina, mitigate LPS-induced retinal RGC damage, inhibit LPS-induced expressions of proinflammatory cytokines TNF-α and IL-6, COX2 and iNOS in the optic nerve injury model of optic neuritis in rats, as well as inhibit the activation of STAT1, STAT3 and NF-κB pathways. Conclusion: LBP can ameliorate optic nerve damage, and the mechanism may be realized through inhibiting NF- B and STAT signaling pathways.

‘Twenty syndrome’ in neuromyelitis optica spectrum disorder

2020 ◽  
Vol 13 (9) ◽  
pp. e234450
Author(s):  
Ritwik Ghosh ◽  
Souvik Dubey ◽  
Subhankar Chatterjee ◽  
Durjoy Lahiri
Keyword(s):  
Optic Neuritis ◽  
Immunosuppressive Therapy ◽  
Neuromyelitis Optica ◽  
Cranial Nerve ◽  
Spectrum Disorder ◽  
Neuromyelitis Optica Spectrum Disorder ◽  
Optic Nerves ◽  
Seventh Cranial Nerve ◽  
Nerve Paresis ◽  
Pons Medulla

A 30-year-old woman presented with recurrent hiccups, vomiting and painful diminution of vision and gait instability for 1 day. She had one-and-a-half syndrome, bilateral seventh cranial nerve paresis with bilateral symptomatic optic neuritis and left-sided ataxic haemiparesis. We described her disorder as the ‘twenty syndrome’ (11/2+7+7+2+2+½=20). MRI of her brain revealed demyelination predominantly in right posterolateral aspect of pons, medulla and bilateral optic nerves. Serum antiaquaporin-4 antibody came out positive. Thus, she was diagnosed as neuromyelitis optica spectrum disorder (NMOSD). She responded brilliantly to immunosuppressive therapy. This is the first ever reported case of the ‘twenty syndrome’ secondary to cerebral NMOSD.

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