Microglia response in retina and optic nerve in chronic experimental autoimmune encephalomyelitis

Horstmann, Lioba; Kuehn, Sandra; Pedreiturria, Xiomara; Haak, Kathrin; Pfarrer, Christiane; Dick, H. Burkhard; Kleiter, Ingo; Joachim, Stephanie C.

doi:10.1016/j.jneuroim.2016.06.008

Cited by 38 publications

(44 citation statements)

References 40 publications

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“…In the present study, we used the mouse model of myelin oligodendrocyte glycoprotein (MOG) immunization that results in EAE with a high incidence of optic neuritis (see [ 22 ]) in order to determine whether nFAG may counteract neuroinflammation with the final aim to address a possible role of this diet supplement in counteracting RGC degeneration. To this aim, nFAG was given daily to animals fed with a standard diet, starting on the day of MOG administration and continuing until their sacrifice, 16 days later.…”

Section: Introductionmentioning

confidence: 99%

Fatty Acids Dietary Supplements Exert Anti-Inflammatory Action and Limit Ganglion Cell Degeneration in the Retina of the EAE Mouse Model of Multiple Sclerosis

et al. 2018

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Optic neuritis is an acute inflammatory demyelinating disorder of the optic nerve (ON) and is an initial symptom of multiple sclerosis (MS). Optic neuritis is characterized by ON degeneration and retinal ganglion cell (RGC) loss that contributes to permanent visual disability and lacks a reliable treatment. Here, we used the experimental autoimmune encephalomyelitis (EAE) mouse model of MS, a well-established model also for optic neuritis. In this model, C57BL6 mice, intraperitoneally injected with a fragment of the myelin oligodendrocyte glycoprotein (MOG), were found to develop inflammation, Müller cell gliosis, and infiltration of macrophages with increased production of oncomodulin (OCM), a calcium binding protein that acts as an atypical trophic factor for neurons enabling RGC axon regeneration. Immunolabeling of retinal whole mounts with a Brn3a antibody demonstrated drastic RGC loss. Dietary supplementation with Neuro-FAG (nFAG®), a balanced mixture of fatty acids (FAs), counteracted inflammatory and gliotic processes in the retina. In contrast, infiltration of macrophages and their production of OCM remained at elevated levels thus eventually preserving OCM trophic activity. In addition, the diet supplement with nFAG exerted a neuroprotective effect preventing MOG-induced RGC death. In conclusion, these data suggest that the balanced mixture of FAs may represent a useful form of diet supplementation to limit inflammatory events and death of RGCs associated to optic neuritis. This would occur without affecting macrophage infiltration and the release of OCM thus favoring the maintenance of OCM neuroprotective role.

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Section: Introductionmentioning

confidence: 99%

Fatty Acids Dietary Supplements Exert Anti-Inflammatory Action and Limit Ganglion Cell Degeneration in the Retina of the EAE Mouse Model of Multiple Sclerosis

et al. 2018

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“…Similar proportions of T cell, B cell, macrophage and microglia populations have been described within the spinal cord and optic nerve 64 . However, there is a lack of immune infiltrates within the choroid or retina surrounding the RGCs, with CD3+ infiltrates exclusively occurring in the optic nerve whereas activated microglia and astrocytes are present in the choroid 12 , 65 . Alternatively, in the spinal cord, CD3+ infiltrates are described in close proximity to motor neurons 11 .…”

Section: Discussionmentioning

confidence: 99%

Neuronal microRNA regulation in Experimental Autoimmune Encephalomyelitis

Juźwik

Drake

Lécuyer

et al. 2018

Sci Rep

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Multiple sclerosis (MS) is an autoimmune, neurodegenerative disease but the molecular mechanisms underlying neurodegenerative aspects of the disease are poorly understood. microRNAs (miRNAs) are powerful regulators of gene expression that regulate numerous mRNAs simultaneously and can thus regulate programs of gene expression. Here, we describe miRNA expression in neurons captured from mice subjected to experimental autoimmune encephalomyelitis (EAE), a model of central nervous system (CNS) inflammation. Lumbar motor neurons and retinal neurons were laser captured from EAE mice and miRNA expression was assessed by next-generation sequencing and validated by qPCR. We describe 14 miRNAs that are differentially regulated in both neuronal subtypes and determine putative mRNA targets though in silico analysis. Several upregulated neuronal miRNAs are predicted to target pathways that could mediate repair and regeneration during EAE. This work identifies miRNAs that are affected by inflammation and suggests novel candidates that may be targeted to improve neuroprotection in the context of pathological inflammation.

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“…All rats were monitored and scored daily from day 0 to 18 p.i. by two independent observers in a blinded manner following the standard 0-5 EAE grading scale as previously published (6,8): 0, natural; 0.5, partial tail paralysis; 1, tail limpness or waddling gait; 1.5, loss of tail tonicity or waddling gait; 2, hind limb weakness; 2.5, partial limb paralysis;…”

Section: Mat Treatment and Disease Assessmentmentioning

confidence: 99%

“…In 15%-20% of individuals who eventually develop MS, ON is their rst sign of disease. An acute, self-limited episode of optic nerve in ammation results in demyelination, accompanied by temporary or permanent loss of vision (6,7).…”

Section: Introductionmentioning

confidence: 99%

Matrine protects retinal ganglion cells from apoptosis in experimental optic neuritis

Kang¹,

Liu²,

Song³

et al. 2020

Preprint

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Background: Inflammatory demyelination and axonal injury of the optic nerve are hallmarks of optic neuritis (ON), which often occurs in multiple sclerosis and is a major cause of visual disturbance in young adults. Although a high dose of corticosteroids can promote visual recovery, it cannot prevent permanent neuronal damage. Novel and effective therapies are thus required. Given the recently defined capacity of matrine (MAT), a quinolizidine alkaloid derived from the herb Radix Sophorae flavescens, in immunomodulation and neuroprotection, we tested in this study the effect of matrine on rats with experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. Results: MAT administration, started at disease onset, significantly suppressed optic nerve infiltration and demyelination, with reduced numbers of Iba1 + macrophages/microglia and CD4 + T cells, compared to those from vehicle-treated rats. Increased expression of neurofilaments, an axon marker, reduced numbers of apoptosis in retinal ganglion cells (RGCs), and reduced numbers of Iba1 + macrophages/microglia and CD4 + T cells were also observed in the retina after MAT treatment. Conclusions: Taken as a whole, our results demonstrate that MAT attenuated inflammation, demyelination and axonal loss in the optic nerve, and protected RGCs from inflammation-induced cell death. MAT may therefore have potential as a novel treatment for this disease that may result in blindness.

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Microglia response in retina and optic nerve in chronic experimental autoimmune encephalomyelitis

Cited by 38 publications

References 40 publications

Fatty Acids Dietary Supplements Exert Anti-Inflammatory Action and Limit Ganglion Cell Degeneration in the Retina of the EAE Mouse Model of Multiple Sclerosis

Fatty Acids Dietary Supplements Exert Anti-Inflammatory Action and Limit Ganglion Cell Degeneration in the Retina of the EAE Mouse Model of Multiple Sclerosis

Neuronal microRNA regulation in Experimental Autoimmune Encephalomyelitis

Matrine protects retinal ganglion cells from apoptosis in experimental optic neuritis

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