Research Applications for Striatech Products

Autoimmune Demyelinating Diseases

Multiple sclerosis, NMOSD, MOGAD, and their experimental analogues — distinct immunopathologies that converge on shared cascades of complement activation, microglial myelin stripping, and secondary axon degeneration.

Introduction

Animal Models

Research Questions

Measurement Modalities

Publications

Journal Clubs

Introduction

What is Autoimmune Demyelinating Diseases?

Autoimmune demyelinating diseases are a family of CNS conditions in which adaptive and innate immune mechanisms converge on myelin, oligodendrocytes, and the axons they insulate, producing recurrent or progressive white matter injury. The group encompasses multiple sclerosis (MS) in its relapsing-remitting and progressive forms, neuromyelitis optica spectrum disorder (NMOSD), MOG antibody-associated disorder (MOGAD), acute disseminated encephalomyelitis (ADEM), and a spectrum of experimental models including the classical MOG_35-55 EAE, MP4 EAE, B cell-dependent EAE, passive-transfer NMOSD, and the Theiler murine encephalomyelitis virus (TMEV) model. Despite their individual immunopathological signatures – T cell-dominant in MS, astrocyte-targeting aquaporin-4 antibodies in NMOSD, MOG-specific IgG in MOGAD – these entities share common downstream effector cascades: complement activation, microglial and macrophage-mediated myelin stripping, secondary axon degeneration, and oligodendrocyte loss. This page focuses specifically on the shared and divergent mechanisms across autoimmune demyelinating entities and their common visual-system translational endpoints, sitting above the narrower disease-specific pages for individual conditions. This topic spans multiple application areas, including: Neuroinflammation and Autoimmune CNS Disease , Ocular Inflammation and Immune-Mediated Eye Disease, Rare and Inherited CNS and Eye Disorders (such as Pelizaeus-Merzbacher disease), and Systemic Aging and CNS Decline. Further relevant are clinical entities such as Optic Neuritis, as well as downstream consequences including Optic Nerve Damage and Axon Degeneration.

Vision: A Window into the brain

Why Are Visual Endpoints Relevant in Autoimmune Demyelinating Diseases Research?

If you work on MS, NMOSD, or MOGAD and do not primarily study the eye, the visual system is still a strategically important endpoint for your preclinical work. The optic nerve is a tract of CNS white matter that is anatomically isolated, optically accessible, and functionally quantifiable. All three major autoimmune demyelinating entities preferentially attack the optic nerve – MS produces optic neuritis in up to 50 percent of patients, NMOSD optic neuritis is typically more severe and bilateral, and MOGAD produces optic neuritis as its most common clinical feature. This convergence is not coincidental: the optic nerve shares the myeloarchitecture and immune access routes of spinal and brain white matter, but adds the practical advantage that its function can be read out non-invasively and repeatedly via optomotor acuity (OptoDrum), pattern ERG, VEP, and OCT-RNFL in the same living animal. For spinal cord or brain-focused MS researchers, this means optic nerve function provides a complementary, quantifiable, non-invasive window on the demyelinating process that does not require terminal endpoints at each time point. OptoDrum in particular measures the subcortical optomotor reflex – a retina-to-brainstem pathway – in awake, freely moving rodents without anaesthesia, enabling repeated longitudinal sampling across relapse and remission cycles, drug washout periods, and aging time courses that would be impractical with invasive endpoints alone.

Animal Models

What Are Common Animal Models For Autoimmune Demyelinating Diseases?

The following models are included because they have direct published evidence linking autoimmune demyelinating mechanisms to functional visual endpoints in the Striatech publication corpus. Models used on parent application areas for broader neuroinflammatory or neuroprotective reasons without a specific autoimmune demyelinating mechanism are deferred to the parent application pages listed above.

MOG_35-55 EAE (T cell-driven, relapsing or monophasic) – The most widely used MS model. Active immunisation with MOG_35-55 peptide in C57BL/6 mice elicits a CD4+ T cell-dominated CNS autoimmune attack. Optic neuritis is a consistent feature; OptoDrum has quantified visual acuity loss and recovery across relapse-remission cycles in this model.
MP4 EAE (chronic progressive; T cell + B cell) – Immunisation with MBP-PLP4 fusion protein produces a chronic progressive demyelinating course that better models the progressive MS phenotype. Visual pathway involvement is documented with OptoDrum-based longitudinal tracking.
B cell-dependent EAE (humoral component; MOG antibody-positive) – A variant model in which B cell responses and MOG-specific antibodies drive demyelination alongside T cell-mediated inflammation, bridging the classical EAE paradigm to MOGAD immunopathology. OptoDrum documents functional visual consequences of the humoral immune attack (Joly et al., 2022, J Neuroinflammation).
NMOSD passive-transfer model (AQP4-IgG) – Passive transfer of aquaporin-4-specific antibodies recapitulates the astrocyte-targeted pathology of NMOSD, including severe optic nerve inflammation. OptoDrum has characterised the functional visual profile of AQP4-antibody-mediated attack, distinguishing it from classical EAE (Remlinger et al., 2023, Neurol Neuroimmunol Neuroinflamm).
CX3CR1 microglial model (aging-demyelination interaction) – A model combining aging and autoimmune inflammation in which microglial CX3CR1 signalling drives optic nerve demyelination. OptoDrum documents functional visual consequences longitudinally, making this model uniquely suited to studying the age-accelerated demyelination axis (Groh et al., 2025, Nat Neurosci).
PLP-deficient model (Pelizaeus-Merzbacher disease; rare inherited demyelination) – PLP1 mutations cause Pelizaeus-Merzbacher disease, an X-linked leukodystrophy. This model provides evidence that microglial demyelination context determines functional outcome even in non-autoimmune demyelinating disease, with OptoDrum tracking visual acuity as a functional correlate of myelination across disease stages (Groh et al., 2023, Nat Commun). For the broader rare inherited demyelinating disease landscape, see Rare and Inherited CNS and Eye Disorders.

Research Questions

How Can Striatech Tools support Your Study?

Select a question that matches your research objective to see which instruments are relevant, what challenge they address, and what the published evidence shows.

How Do MS, NMOSD, and MOGAD Differ in Their Immune Mechanisms and Visual Phenotypes, and Which Preclinical Models Best Capture Each?

Audience A - Vision-focused

Audience B - CNS/Systemic

Quick Answer

MS, NMOSD, and MOGAD engage distinct immune effectors – CD4+ T cells and intermittent B cell activity in MS, AQP4-targeting IgG and complement in NMOSD, MOG-specific IgG in MOGAD – and produce distinguishable optic nerve and visual functional profiles. OptoDrum captures these phenotypic differences non-invasively in the corresponding rodent models, with NMOSD and MOGAD models documented to produce more severe and less remitting visual deficits than classical MOG_35-55 EAE. For the detailed time course of visual acuity loss and recovery in EAE-optic neuritis, see Optic Neuritis.

The challenge

A key translational problem in the demyelinating disease field is that many preclinical studies use classical MOG_35-55 EAE as a generic demyelinating disease proxy, when in fact MS, NMOSD, and MOGAD differ substantially in the immune compartments driving damage. NMOSD is driven primarily by AQP4-specific antibodies that activate complement and recruit granulocytes to attack astrocytes, producing more severe and often bilateral optic neuritis with poor recovery. MOGAD involves MOG-specific IgG that targets the oligodendrocyte surface, producing a more pronounced humoral attack on myelin itself. MS combines T cell-driven inflammation with a substantial B cell and antibody component, particularly in its progressive forms.

This heterogeneity means that a treatment effective in MOG_35-55 EAE may not translate to NMOSD or MOGAD. The visual system provides a common functional endpoint across these entities: optic neuritis is a cardinal feature of all three, and OptoDrum-measured visual acuity provides a model-agnostic readout of the severity and recovery of optic nerve injury. However, using the same model for all three diseases conflates their distinct mechanisms and fails to predict treatment response in the clinic. For a broader overview of how neuroinflammatory mechanisms drive visual dysfunction, see Neuroinflammation.

How Striatech products help

OptoDrum

Measures spatial visual acuity (cycles per degree) and contrast sensitivity via the subcortical optomotor reflex in awake, freely moving rodents. Provides the primary non-invasive functional readout for comparing the severity and recovery trajectory of optic neuritis across MOG_35-55 EAE, B cell-dependent EAE, NMOSD passive-transfer, and MOGAD models without anaesthesia or operator bias. Enables repeated measurements across the full disease course in the same animals.

AcuiSee

Measures visual acuity via a cortical operant paradigm requiring learned visual discrimination. Complements OptoDrum by assessing the cortical visual processing dimension of demyelinating disease, which includes the integrity of retino-cortical projections and V1 processing downstream of the optic nerve. Particularly relevant for chronic progressive models where cortical reorganisation or visual plasticity may buffer the OMR response while cortical function remains impaired.

Non-aversive Animal Platform

Reduces handling-stress confounds during functional measurements in EAE animals, which exhibit motor and autonomic dysfunction that can elevate corticosterone and confound visual assessment. Particularly relevant for comparing acuity across disease groups where motor scores differ substantially.

Evidence from the Literature

Kinuthia et al (2025) JCI Insight.
Remlinger et al (2023) Neurol. Neuroimmunol. Neuroinflamm.
Developed and characterised EAE-based rodent models for NMOSD and MOGAD, using OptoDrum (Striatech) to establish the distinct functional visual profiles of AQP4-antibody and MOG-antibody-mediated optic pathway attack.
Joly et al (2022) J. Neuroinflammation
Characterised a B cell-dependent EAE model incorporating MOG-specific antibody responses that bridge the MS and MOGAD spectra. OptoDrum (Striatech) documented the functional visual consequence of B cell/antibody-driven demyelination, establishing that humoral autoimmunity produces a distinct OMR-measurable visual phenotype from purely T cell-driven models.

What Shared Mechanisms of T Cell, B Cell, and Antibody-Mediated Injury Operate Across Autoimmune Demyelinating Syndromes, and How Are They Captured with Functional Visual Endpoints?

Audience A - Vision-focused

Audience B - CNS/Systemic

Quick Answer

Despite their entity-specific immunopathology, MS, NMOSD, MOGAD, and ADEM converge on shared downstream effectors: complement activation, RGC death, axon degeneration, and oligodendrocyte loss. Preclinical models spanning T cell-dominant, B cell-dependent, and antibody-transfer designs allow these mechanisms to be dissected individually while using OptoDrum and OCT as shared functional readouts. For the tissue-level consequences of demyelinating axon injury, see Optic Nerve Damage and Axon Degeneration.

The challenge

A critical unresolved question in demyelinating disease research is whether the downstream effectors of axon damage are sufficiently conserved across MS, NMOSD, and MOGAD to justify the same neuroprotective strategies across diseases, or whether disease-specific immune mechanisms produce distinct axonal injury signatures requiring tailored interventions. In MS, the primary T cell wave is followed by secondary oligodendrocyte apoptosis and Wallerian axon degeneration; in NMOSD, complement-driven astrocyte loss leads to a bystander axon injury pattern; in MOGAD, MOG-IgG at the oligodendrocyte surface may trigger a more direct myelin stripping with preserved axon integrity in early stages. Functionally quantifying these differences – and whether they produce different OMR trajectories – is a prerequisite for rational target selection across the disease spectrum.

A particularly important shared mechanism is microglia-mediated myelin processing, whose role has been reframed from uniformly pathological to context-dependent. Groh et al. (2023) demonstrated that microglial demyelination in the PLP-deficient model is protective, preserving axon integrity and visual function, while Groh et al. (2025) demonstrated that CX3CR1-dependent microglial activation in an aging-autoimmune model drives destructive optic nerve demyelination. This dual biology – protective vs pathological microglial demyelination – is a cross-entity mechanism with direct relevance to therapeutic targeting of microglia in MS, NMOSD, and MOGAD.

How Striatech products help

OptoDrum

Provides a non-invasive functional readout that integrates the cumulative effect of demyelination, axon degeneration, and RGC loss on the retino-brainstem pathway. Enables direct comparison of the functional severity of different immune attack modalities (T cell, B cell, antibody) in the same output metric (cycles per degree), supporting cross-disease mechanistic comparison in the same cohort design.

AcuiSee

Assesses cortical visual function, which may be preserved when subcortical pathways are compromised or vice versa. Adding the AcuiSee cortical endpoint alongside OptoDrum allows dissociation of subcortical and cortical visual pathway vulnerability in demyelinating models.

DarkAdapt

Provides controlled dark-adaptation prior to scotopic OMR testing with the ScotopicKit, enabling assessment of rod-mediated visual pathways. Relevant when demyelinating disease models produce selective rod or cone pathway involvement detectable via scotopic vs photopic OMR comparison.

Evidence from the Literature

Kinuthia et al (2025) JCI Insight.
Groh et al (2023) Nat Commun.
Feature →
Demonstrated that controlled microglial demyelination is protective rather than damaging in PLP1-deficient mice, using OptoDrum (Striatech) to show preserved visual function when microglial myelin removal was intact. Establishes the context-dependence of microglial demyelination as a cross-entity mechanism relevant to MS and genetic leukodystrophy, relevant to both autoimmune and genetic demyelinating diseases.

How Can Visual-Function Endpoints Benchmark Disease-Modifying and Neuroprotective Therapies Across Multiple Autoimmune Demyelinating Models?

Audience A - Vision-focused

Audience B - CNS/Systemic

Quick Answer

OptoDrum-measured spatial acuity serves as a model-agnostic translational endpoint for evaluating treatment efficacy in EAE, NMOSD, and MOGAD preclinical models. Three published studies using OptoDrum document preserved visual function after HIF-1 inhibition (metabolic-inflammatory interface), FcRn antibody depletion (immunoglobulin clearance), and histaminergic modulation (neuroimmune communication), spanning mechanistically distinct therapeutic strategies on a single comparable endpoint.

The challenge

Preclinical demyelinating disease therapy benchmarking is hampered by the use of different readouts across studies – motor clinical scoring in EAE, histological axon counts, or electrophysiological VEP – that are difficult to compare across laboratories or disease models and poorly predict clinical visual outcomes. The need for a standardised functional visual endpoint that (1) is non-invasive, (2) can be repeated longitudinally, (3) is quantitative and operator-independent, and (4) integrates the net effect of demyelination and neuroprotection on a visual circuit is acute. OptoDrum fills this role: because the optomotor reflex depends on the integrity of the entire retina-to-brainstem pathway, it captures the integrated consequence of treatment effects at any level from oligodendrocyte survival to axon preservation to RGC survival.

An additional challenge is that different therapeutic strategies target different immune compartments – T cell suppression, B cell depletion, antibody clearance, metabolic rescue, microglial modulation – and the relative contribution of each varies by disease entity. An endpoint that is equally sensitive to all these mechanisms enables their comparison within a unified experimental framework.

How Striatech products help

OptoDrum

Provides the primary functional efficacy endpoint for therapy benchmarking: spatial visual acuity (cycles per degree) measured repeatedly in the same animals throughout the treatment period. Operator-independent and fully automated, supporting blinded efficacy assessment across treatment groups without the subjectivity of clinical motor scoring or histological cell counting.

AcuiSee

Adds a cortical operant acuity endpoint that may detect residual cortical visual function impairment not captured by the subcortical OMR, particularly in chronic progressive models where cortical adaptation could mask the OptoDrum treatment signal.

Non-aversive Animal Platform

Minimises handling stress during repeated functional measurements across treatment groups, reducing corticosterone-driven confounds that may differ between immunosuppressed and control animals.

Evidence from the Literature

Kinuthia et al (2025) JCI Insight.
Anders et al (2023) Front Immunol.
Demonstrated that pharmacological HIF-1 inhibition reduces optic nerve hypoxia and preserves visual acuity in EAE, using OptoDrum (Striatech) as the primary functional endpoint. Establishes the metabolic-inflammatory interface as a druggable axis for visual neuroprotection in demyelinating disease.
Remlinger et al (2022) Neurol. Neuroimmunol. Neuroinflamm.
Journal Club →
Validated FcRn blockade (efgartigimod class) as a strategy for reducing circulating MOG-IgG and attenuating antibody-mediated optic neuritis in an EAE/MOGAD model, with OptoDrum (Striatech) documenting visual function preservation as the translational functional endpoint.
Morin et al (2021) J. Immunol.
Feature →
Used conditional deletion of histidine decarboxylase in specific immune cell populations to demonstrate that histaminergic signalling modulates EAE severity and functional visual outcomes, with OptoDrum (Striatech) confirming that histamine pathway manipulation alters OMR-measured visual acuity. Establishes the histaminergic neuroimmune axis as a pharmacologically accessible target in autoimmune demyelinating disease.

How Does Aging Amplify Autoimmune Demyelinating Damage, and What Do Longitudinal Optomotor Trajectories Reveal About the Age-Accelerated Disease Course?

Audience A - Vision-focused

Audience B - CNS/Systemic

Quick Answer

Aging drives two reinforcing mechanisms that amplify demyelinating damage: immunosenescence-driven CD8+ T cell accumulation in CNS white matter and CX3CR1-dependent microglial senescence that shifts microglia from a homeostatic to a pro-inflammatory optic nerve-demyelinating phenotype. Both mechanisms have been quantified with OptoDrum as the longitudinal functional visual endpoint, producing progressive acuity decline superimposed on or accelerating the autoimmune demyelinating injury. For the broader aging-CNS decline context, see Systemic Aging and CNS Decline.

The challenge

The majority of preclinical MS and autoimmune demyelinating disease research uses young adult animals (8-12 weeks), yet the clinical disease course of MS is substantially modified by aging: secondary progressive MS is age-dependent, older patients have worse recovery from relapses, and primary progressive MS is predominantly a disease of midlife and beyond. The biological mechanisms underlying age-acceleration of demyelinating disease are incompletely understood but implicate immunosenescence (altered T cell repertoire, accumulation of exhausted or cytotoxic CD8+ T cells in white matter), microglial senescence (reduced homeostatic surveillance, amplified CX3CR1-dependent inflammatory activation), and reduced oligodendrocyte precursor cell regenerative capacity.

Functionally capturing the aging-demyelination interaction requires longitudinal endpoints that can be applied repeatedly across months in aging cohorts without the cumulative invasiveness of anaesthesia-dependent methods. OptoDrum meets this requirement: measurements take minutes per animal without sedation, enabling weekly or monthly tracking of visual acuity decline in aging EAE or aging-microglial-activation cohorts alongside younger controls.

How Striatech products help

OptoDrum

Provides repeated, non-invasive spatial visual acuity measurements suitable for months-long aging cohort studies. Documents the progressive acuity decline driven by immunosenescence-associated CD8+ T cell accumulation and age-related CX3CR1-dependent microglial optic nerve demyelination. The subcortical optomotor reflex is robust to normal aging-associated motor slowing, making it a reliable longitudinal endpoint in aged animals.

Non-aversive Animal Platform

Particularly relevant for aged or debilitated animals, who may have difficulty with conventional restraint. The platform-free design minimises stress-response confounds that are disproportionately large in aged animals with dysregulated HPA axes, improving data quality in longitudinal aging-demyelination studies.

AcuiSee

The cortical operant paradigm may detect age-related cortical visual processing decline separately from the subcortical OMR signal, allowing dissociation of aging effects on cortical vs subcortical visual pathways in demyelinating disease cohorts.

Evidence from the Literature

Kinuthia et al (2025) JCI Insight.
Groh et al (2025) Nat Neurosci.
Journal Club →
Feature →
Demonstrated that age-related microglial activation via CX3CR1 drives optic nerve demyelination and RGC death, with OptoDrum (Striatech) documenting the functional visual decline in aged autoimmune animals. Establishes CX3CR1-dependent microglial senescence as a mechanistic amplifier of age-accelerated demyelinating optic nerve injury.
Groh et al (2021) Nat. Aging
Journal Club →
Demonstrated that CD8+ cytotoxic T cells accumulate progressively in aged CNS white matter and drive axon degeneration, using OptoDrum (Striatech) to track the functional visual consequence longitudinally as a biomarker of immunosenescence-driven neuroinflammation. Provides the foundational evidence for adaptive immune aging as a driver of demyelinating visual pathway decline.

How Does Microglial Biology Define the Functional Outcome of Demyelination – Protective Versus Pathological – and What Visual Endpoints Distinguish These Roles Across Autoimmune Demyelinating Models?

Audience A - Vision-focused

Audience B - CNS/Systemic

Quick Answer

Microglia are not uniformly protective or pathological in demyelination: context and signalling state determine whether their myelin-processing activity preserves or destroys axons. OptoDrum has documented both outcomes in directly comparable visual acuity measurements – protective microglial demyelination in PLP-deficient mice maintaining visual function, and CX3CR1-driven pathological demyelination in an aging-autoimmune model producing progressive acuity loss. This dual biology has direct relevance to the translational question of whether microglial-targeting therapies in MS and MOGAD should suppress or modulate microglia.

The challenge

Microglia-targeting is one of the most active therapeutic strategies in CNS demyelinating disease, with agents ranging from CSF1R inhibitors (suppressive) to BTK inhibitors (modulatory) entering clinical development for MS. A central challenge is that preclinical studies have produced contradictory evidence: some show that microglial depletion or suppression worsens remyelination by removing myelin debris; others show that microglial activation drives axon loss and clinical worsening. This contradiction reflects genuine biological context-dependence rather than model artefact.

The Groh et al. laboratory has produced the most direct published evidence of this duality within the autoimmune demyelinating disease context, using the same functional endpoint (OptoDrum-measured visual acuity) in both a protective and a destructive microglial demyelination scenario. Groh 2023 established protective microglial demyelination in the PLP1-deficient genetic model; Groh 2025 established pathological CX3CR1-dependent microglial demyelination in an aging-autoimmune model. The fact that both were captured with the same OptoDrum endpoint enables direct functional comparison across contexts and models.

How Striatech products help

OptoDrum

Provides a shared functional currency for comparing protective and pathological microglial outcomes: visual acuity in cycles per degree, measured non-invasively at matched time points across different demyelinating model systems. Enables direct numerical comparison of functional outcomes between microglial suppression, activation, and context-specific manipulation experiments without confounds from interspecies or inter-assay variability.

AcuiSee

Cortical operant visual acuity provides a complementary endpoint that assesses whether microglial manipulation effects on subcortical visual pathways propagate to cortical processing, relevant when CX3CR1 or CSF1R-dependent microglial states affect higher visual areas beyond the optic nerve.

Evidence from the Literature

Kinuthia et al (2025) JCI Insight.
Groh et al (2025) Nat Neurosci.
Journal Club →
Feature →
Established the pathological side of microglial duality: CX3CR1-dependent microglial activation drives optic nerve demyelination and RGC death in an aging-autoimmune context, documented with OptoDrum (Striatech) as the functional visual endpoint.
Groh et al (2023) Nat Commun.
Feature →
Established the protective side of microglial duality: controlled microglia-mediated myelin removal in PLP1-deficient mice prevents secondary axon degeneration and preserves visual acuity measured by OptoDrum (Striatech).

Product Fit

Summary: Striatech Products supporting your research questions

Research Question	OptoDrum	AcuiSee	DarkAdapt	Non-aversive platform
Cross-disease visual phenotype comparison (MS vs NMOSD vs MOGAD)	Yes	Yes		Yes
Shared T cell / B cell / antibody injury mechanisms	Yes	Yes	Yes	Yes
Disease-modifying therapy benchmarking	Yes	Yes		Yes
Aging-demyelination interaction (longitudinal)	Yes	Yes		Yes
Microglial dual-role demyelination context	Yes	Yes

Notes: ScotopicKit is applicable if rod-pathway visual function is an explicit study endpoint in scotopic EAE or NMOSD protocols. Photorefractor and Keratometer measure refractive state and corneal curvature respectively, and are not relevant to the primarily axonal and retinal endpoints.

Measurement Modalities

Measuring Functional Visual Outcomes in Autoimmune Demyelinating Diseases: How Do Available Methods Compare?

Autoimmune demyelinating disease preclinical research employs a range of visual and neurological readouts. The table below summarises the main modalities, with an emphasis on the dimensions most relevant to cross-disease functional comparison and longitudinal study design.

Modality	What It Measures	Invasiveness	Repeatability in the same animal	Cross-model comparability	3Rs relevance
OptoDrum (Striatech)	Spatial visual acuity and contrast sensitivity via optomotor reflex (subcortical retina-to-brainstem)	Non-invasive; no anaesthesia	High; daily or weekly possible	High; identical metric across EAE, NMOSD, MOGAD, and aging models	Refinement (no restraint, no anaesthesia); enables Reduction by replacing terminal cohorts for functional readouts
AcuiSee (Striatech)	Visual acuity via operant forced-choice paradigm (cortical processing required)	Non-invasive; food restriction required for motivation	High after training phase (10-14 days)	High; cortical complement to OptoDrum across models	Refinement; provides psychophysical cortical endpoint; no anaesthesia
Visual Evoked Potential (VEP)	Cortical response to visual stimulation; latency and amplitude reflect retino-cortical conduction and demyelination severity	Invasive; surgical electrode implantation typically required	Low to moderate depending on implant	Moderate; latency changes specifically sensitive to demyelination; widely used in MS trials as a translational endpoint	Lower 3Rs score due to surgical invasiveness; complements OMR for the cortical and conduction dimension
Optical coherence tomography (OCT)	Retinal nerve fibre layer (RNFL) and ganglion cell layer (GCL) thickness; structural endpoint only	Low to moderate; typically requires anaesthesia or restraint in rodents	High	High; RNFL thinning is a validated MS biomarker in both clinical and preclinical use	Structural endpoint; does not measure functional vision; complements OMR for structure-function correlation
EAE clinical motor scoring	Hind-limb paralysis and body weight; reflects spinal cord involvement	Non-invasive	High	Low; scores are not directly comparable across induction protocols or disease entities	Moderate; does not capture visual pathway involvement; subjective and scale-dependent
Histological RGC and axon counting	RGC soma and optic nerve axon density at a single terminal time point	Terminal	None	Moderate; consistent across models if methodology is standardised	Terminal; complements repeated OMR measurements as the structural correlate at study end

Supported by Striatech Products

Publications on Autoimmune Demyelinating Diseases

Nature Neuroscience (Jun 28, 2025) Microglia activation orchestrates CXCL10-mediated CD8+ T cell recruitment to promote aging-related white matter degeneration

Groh J, Feng R, Yuan X, Liu L, Klein D, Hutahaean G, Butz E, Wang Z, Steinbrecher L, Neher J, Martini R, Simons M.

DOI: 10.1038/s41593-025-01955-w >>

Journal Club

Featured Publication

Featured image for “When Brain Defenders Turn Destructive: How Microglia and T Cells Promote Age-Related Decline”

As we get older, immune cells in the brain called microglia can become overactive and attract aggressive CD8+ T cells. These T cells then attack the brain’s axons’ protective layer, known as myelin, leading to its damage and a decline in brain function. Groh et al reveal the chain reaction behind these age-related brain changes and point to new opportunities for preventing or slowing down brain degeneration. The OptoDrum assay confirmed the link between axon degeneration and behavioral vision deficits.

Aging is the major risk factor for neurodegeneration and is associated with structural and functional alterations in white matter. Myelin is particularly vulnerable to aging, resulting in white matter-associated microglia activation. Here we used pharmacological and genetic approaches to investigate microglial functions related to aging-associated changes in myelinated axons of mice. Our results reveal that maladaptive microglia activation promotes the accumulation of harmful CD8⁺ T cells, leading to the degeneration of myelinated axons and subsequent impairment of brain function and behavior. We characterize glial heterogeneity and aging-related changes in white matter by single-cell and spatial transcriptomics and reveal elaborate glial-immune interactions. Mechanistically, we show that the CXCL10-CXCR3 axis is crucial for the recruitment and retention of CD8⁺ T cells in aged white matter, where they exert pathogenic effects. Our results indicate that myelin-related microglia dysfunction promotes adaptive immune reactions in aging and identify putative targets to mitigate their detrimental impact.

Related Products:

OptoDrum

Applications:
Aging
·
Autoimmune Demyelinating Diseases
·
Glial Suppression
·
Neuroinflammation and Autoimmune CNS Disease
·
Ocular Inflammation and Immune-Mediated Eye Disease
·
Optic Nerve Damage
·
Optic Neuritis
·
Retinal Ganglion Cell Pathology
·
Systemic Aging and CNS decline
>

Nature Communications (Oct 30, 2023) Microglia-mediated demyelination protects against CD8+ T cell-driven axon degeneration in mice carrying PLP defects

Groh J, Abdelwahab T, Kattimani Y, Hörner M, Loserth S, Gudi V, Adalbert R, Imdahl F, Saliba AE, Coleman M, Stangel M, Simons M, Martini R

DOI: 10.1038/s41467-023-42570-2 >>

Featured Publication

Featured image for “Microglia-mediated Demyelination as a Protective Mechanism in CNS Neurodegeneration”

Groh et al challenge the conventional understanding of myelin diseases by demonstrating that persistent encasement with damaged myelin can be more detrimental to axons than complete demyelination. They found that axon-al damage driven by cytotoxic T cells is less likely to progress to degeneration when axons are efficiently demyelinated by activated microglia. These findings identify harmful interactions between axons, glia, and immune cells that promote neurodegeneration, revealing potential therapeutic targets for myelin-related disorders. The OptoDrum device was utilized to assess visual acuity in mice, providing an unbiased behavioral quantification of functional decline resulting from the observed neurodegeneration.

Axon degeneration and functional decline in myelin diseases are often attributed to loss of myelin but their relation is not fully understood. Perturbed myelinating glia can instigate chronic neuroinflammation and contribute to demyelination and axonal damage. Here we study mice with distinct defects in the proteolipid protein 1 gene that develop axonal damage which is driven by cytotoxic T cells targeting myelinating oligodendrocytes. We show that persistent ensheathment with perturbed myelin poses a risk for axon degeneration, neuron loss, and behavioral decline. We demonstrate that CD8⁺ T cell-driven axonal damage is less likely to progress towards degeneration when axons are efficiently demyelinated by activated microglia. Mechanistically, we show that cytotoxic T cell effector molecules induce cytoskeletal alterations within myelinating glia and aberrant actomyosin constriction of axons at paranodal domains. Our study identifies detrimental axon-glia-immune interactions which promote neurodegeneration and possible therapeutic targets for disorders associated with myelin defects and neuroinflammation.

Related Products:

OptoDrum

Applications:
Autoimmune Demyelinating Diseases
·
Axon Degeneration
·
Neuroinflammation
·
Neuroinflammation and Autoimmune CNS Disease
·
Ocular Inflammation and Immune-Mediated Eye Disease
·
Optic Nerve Damage
·
Optic Neuritis
·
PLP defects
·
Rare and Inherited CNS and Eye Disorders
>

Frontiers in Immunology (Oct 22, 2023) Acriflavine, a HIF-1 inhibitor, preserves vision in an experimental autoimmune encephalomyelitis model of optic neuritis

Anders JJ, Elwood BW, Kardon RH, Gramlich OW

DOI: 10.3389/fimmu.2023.1271118 >>

Featured image for “Acriflavine, a HIF-1 inhibitor, preserves vision in an experimental autoimmune encephalomyelitis model of optic neuritis”

Optic neuritis is often an early sign associated with multiple sclerosis. This study investigated the potential of acriflavine (ACF), a HIF-1 inhibitor, in treating optic neuritis. Using a mouse model of the disease, ACF treatment improved motorsensory function and preserved visual acuity. The treatment also protected retinal ganglion cells and their axons, reduced inflammation, and decreased demyelination in the optic nerve. ACF’s effectiveness was attributed to its inhibition of HIF-1 and interaction with the unfolded protein response pathway. The OptoDrum was used to measure visual acuity in the mice, providing crucial data on the preservation of visual function that contributed to demonstrating ACF’s potential as a therapeutic approach for multiple sclerosis rehabilitation.

Introduction: Optic neuritis (ON) is often an early sign of multiple sclerosis (MS), and recent studies show a link between HIF-1 pathway activation and inflammation. This study aimed to determine if inhibition of the HIF-1 pathway using the HIF-1a antagonist acriflavine (ACF) can reduce clinical progression and rescue the ocular phenotype in an experimental autoimmune encephalomyelitis (EAE) ON model. Methods: EAE-related ON was induced in 60 female C57BL/6J mice by immunization with MOG33-55, and 20 EAE mice received daily systemic injections of ACF at 5 mg/kg. Changes in the visual function and structure of ACF-treated EAE mice were compared to those of placebo-injected EAE mice and naïve control mice. Results: ACF treatment improved motor–sensory impairment along with preserving visual acuity and optic nerve function. Analysis of retinal ganglion cell complex also showed preserved thickness correlating with increased survival of retinal ganglion cells and their axons. Optic nerve cell infiltration and magnitude of demyelination were decreased in ACF-treated EAE mice. Subsequent in vitro studies revealed improvements not only attributed to the inhibition of HIF-1 but also to previously unappreciated interaction with the eIF2a/ATF4 axis in the unfolded protein response pathway. Discussion: This study suggests that ACF treatment is effective in an animal model of MS via its pleiotropic effects on the inhibition of HIF-1 and UPR signaling, and it may be a viable approach to promote rehabilitation in MS.

Related Products:

OptoDrum

Applications:
Autoimmune Demyelinating Diseases
·
Experimental Autoimmune Encephalomyelitis
·
Multiple Sclerosis
·
Neuroinflammation
·
Neuroinflammation and Autoimmune CNS Disease
·
Ocular Inflammation and Immune-Mediated Eye Disease
·
Optic Neuritis
·
Retinal Ganglion Cell Pathology
>

Neurology Neuroimmunology Neuroinflammation (Jul 10, 2023) Modeling MOG Antibody-Associated Disorder and Neuromyelitis Optica Spectrum Disorder in Animal Models: Visual System Manifestations

Remlinger J, Bagnoud M, Meli I, Massy M, Hoepner R, Linington C, Chan A, Bennett JL, Enzmann V, Salmen A

DOI: 10.1212/NXI.0000000000200141 >>

Featured image for “Modeling MOG Antibody-Associated Disorder and Neuromyelitis Optica Spectrum Disorder in Animal Models: Visual System Manifestations”

This study investigated visual impairment mechanisms in two animal models of multiple sclerosis, neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disorder (MOGAD). Researchers first induced experimental autoimmune encephalomyelitis in mice and administered specific antibodies to mimic these conditions. They assessed visual acuity, retinal thickness, and optic nerve pathology over time. Results showed decreased visual acuity and retinal ganglion cell loss in both models, with earlier optic nerve inflammation in the NMOSD model. Visual acuity was measured with the OptoDrum to understand the progression of visual impairment in these disorders.

Background and objectives: Mechanisms of visual impairment in aquaporin 4 antibody (AQP4-IgG) seropositive neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody (MOG-IgG)-associated disorder (MOGAD) are incompletely understood. The respective impact of optic nerve demyelination and primary and secondary retinal neurodegeneration are yet to be investigated in animal models. Methods: Active MOG_35-55 experimental autoimmune encephalomyelitis (EAE) was induced in C57BL/6Jrj mice, and monoclonal MOG-IgG (8-18C5, murine), recombinant AQP4-IgG (rAb-53, human), or isotype-matched control IgG (Iso-IgG, human) was administered 10 days postimmunization. Mobility impairment was scored daily. Visual acuity by optomotor reflex and ganglion cell complex thickness (GCC, 3 innermost retinal layers) by optical coherence tomography (OCT) were longitudinally assessed. Histopathology of optic nerve and retina was investigated during presymptomatic, acute, and chronic disease phases for immune cells, demyelination, complement deposition, natural killer (NK) cell, AQP4, and astrocyte involvement, retinal ganglion cells (RGCs), and Müller cell activation. Groups were compared by nonparametric tests with a p value <0.05 indicating statistical significance. Results: Visual acuity decreased from baseline to chronic phase in MOG-IgG (mean ± standard error of the mean: 0.54 ± 0.01 to 0.46 ± 0.02 cycles/degree, p < 0.05) and AQP4-IgG EAE (0.54 ± 0.01 to 0.43 ± 0.02, cycles/degree, p < 0.05). Immune cell infiltration of optic nerves started in presymptomatic AQP4-IgG, but not in MOG-IgG EAE (5.85 ± 2.26 vs 0.13 ± 0.10 macrophages/region of interest [ROI] and 1.88 ± 0.63 vs 0.15 ± 0.06 T cells/ROI, both p < 0.05). Few NK cells, no complement deposition, and stable glial fibrillary acid protein and AQP4 fluorescence intensity characterized all EAE optic nerves. Lower GCC thickness (Spearman correlation coefficient r = -0.44, p < 0.05) and RGC counts (r = -0.47, p < 0.05) correlated with higher mobility impairment. RGCs decreased from presymptomatic to chronic disease phase in MOG-IgG (1,705 ± 51 vs 1,412 ± 45, p < 0.05) and AQP4-IgG EAE (1,758 ± 14 vs 1,526 ± 48, p < 0.01). Müller cell activation was not observed in either model. Discussion: In a multimodal longitudinal characterization of visual outcome in animal models of MOGAD and NMOSD, differential retinal injury and optic nerve involvement were not conclusively clarified. Yet optic nerve inflammation was earlier in AQP4-IgG-associated pathophysiology. Retinal atrophy determined by GCC thickness (OCT) and RGC counts correlating with mobility impairment in the chronic phase of MOG-IgG and AQP4-IgG EAE may serve as a generalizable marker of neurodegeneration.

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Journal of Neuroinflammation (Feb 23, 2022) B cell-dependent EAE induces visual deficits in the mouse with similarities to human autoimmune demyelinating diseases

Joly S, Mdzomba JB, Rodriguez L, Morin F, Vallières L, Pernet V

DOI: 10.1186/s12974-022-02416-y >>

Featured image for “B cell-dependent EAE induces visual deficits in the mouse with similarities to human autoimmune demyelinating diseases”

The experimental autoimmune encephalomyelitis (EAE) mouse model is commonly used to study visual impairments associated with autoimmune demyelinating diseases. EAE is classically induced by immunization with the peptide MOG35-55. This mouse model lacks certain characteristics of analog diseases in humans, in particular the participation of B-cells in the immune response. Joly et al characterize the effects of immunization with a different peptide, bMOG, and find that these mice show hallmarks of common human diseases, such as multiple sclerosis and neuromyelitis optica. This new mouse model therefore offers new avenues to test protective or restorative ophthalmic treatments.

Background: In the field of autoimmune demyelinating diseases, visual impairments have extensively been studied using the experimental autoimmune encephalomyelitis (EAE) mouse model, which is classically induced by immunization with myelin oligodendrocyte glycoprotein peptide (MOG35-55). However, this model does not involve B cells like its human analogs. New antigens have thus been developed to induce a B cell-dependent form of EAE that better mimics human diseases. Methods: The present study aimed to characterize the visual symptoms of EAE induced with such an antigen called bMOG. After the induction of EAE with bMOG in C57BL/6J mice, visual function changes were studied by electroretinography and optomotor acuity tests. Motor deficits were assessed in parallel with a standard clinical scoring method. Histological examinations and Western blot analyses allowed to follow retinal neuron survival, gliosis, microglia activation, opsin photopigment expression in photoreceptors and optic nerve demyelination. Disease effects on retinal gene expression were established by RNA sequencing. Results: We observed that bMOG EAE mice exhibited persistent loss of visual acuity, despite partial recovery of electroretinogram and motor functions. This loss was likely due to retinal inflammation, gliosis and synaptic impairments, as evi-denced by histological and transcriptomic data. Further analysis suggests that the M-cone photoreceptor pathway was also affected. Conclusion: Therefore, by documenting visual changes induced by bMOG and showing similarities to those seen in diseases such as multiple sclerosis and neuromyelitis optica, this study offers a new approach to test protective or restorative ophthalmic treatments.

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Neurology: Neuroimmunology & Neuroinflammation (Jan 13, 2022) Antineonatal Fc Receptor Antibody Treatment Ameliorates MOG-IgG-Associated Experimental Autoimmune En-cephalomyelitis

Remlinger J, Madarasz A, Guse K, Hoepner R, Bagnoud M, Meli I, Feil M, Abegg M, Linington C, Shock A, Boroojerdi B, Kiessling P, Smith B, Enzmann V, Chan A, Salmen A

DOI: 10.1212/NXI.0000000000001134 >>

Journal Club

Featured image for “Antineonatal Fc Receptor Antibody Treatment Ameliorates MOG-IgG-Associated Experimental Autoimmune En-cephalomyelitis”

Demyelinating autoimmune diseases usually impact the optic nerve and thus visual abilities. Optomotor reflex measurements can therefore be used to non-invasively monitor disease progression and treatment efficacy. Remlinger et al studied MOGAD, a rare autoimmune demyelinating CNS disorder, in a murine model of experimental autoimmune encephalomyelitis (EAE). They assessed the effects of treating those mice with monoclonal antibodies against the neonatal Fc receptor and found that this treatment reduced the severity of the disease. Measurements of visual acuity with Striatech’s OptoDrum correlated well with other disease markers.

Background and Objectives Myelin oligodendrocyte glycoprotein antibody–associated disorder (MOGAD) is a rare, autoimmune demyelinating CNS disorder, distinct from multiple sclerosis and neuromyelitis optica spectrum disor-der. Characterized by pathogenic immunoglobulin G (IgG) antibodies against MOG, a potential treatment strategy for MOGAD is to reduce circulating IgG levels, e.g., by interference with the IgG recycling pathway mediated by the neonatal Fc receptor (FcRn). Although the optic nerve is often detrimentally involved in MOGAD, the effect of FcRn blockade on the visual pathway has not been assessed. Our objective was to investigate effects of a monoclonal an-ti-FcRn antibody in murine MOG-IgG–associated experimental autoimmune encephalomyelitis (EAE). Methods We induced active MOG35-55 EAE in C57Bl/6 mice followed by the application of a monoclonal MOG-IgG (8-18C5) 10 days postimmunization (dpi). Animals were treated with either a specific monoclonal antibody against FcRn (α-FcRn, 4470) or an isotype-matched control IgG on 7, 10, and 13 dpi. Neurologic disability was scored daily on a 10-point scale. Visual acuity was assessed by optomotor reflex. Histopathologic hallmarks of disease were as-sessed in the spinal cord, optic nerve, and retina. Immune cell infiltration was visualized by immunohistochemistry, demyelination by Luxol fast blue staining and complement deposition and number of retinal ganglion cells by im-munofluorescence. Results In MOG-IgG–augmented MOG35-55 EAE, anti-FcRn treatment significantly attenuated neurologic disability over the course of disease (mean area under the curve and 95% confidence intervals (CIs): α-FcRn [n = 27], 46.02 [37.89–54.15]; isotype IgG [n = 24], 66.75 [59.54–73.96], 3 independent experiments), correlating with reduced amounts of demyelination and macrophage infiltration into the spinal cord. T- and B-cell infiltration and comple-ment deposition remained unchanged. Compared with isotype, anti-FcRn treatment prevented reduction of visual acuity over the course of disease (median cycles/degree and interquartile range: α-FcRn [n = 16], 0.50 [0.48–0.55] to 0.50 [0.48–0.58]; isotype IgG [n = 17], 0.50 [0.49–0.54] to 0.45 [0.39–0.51]). Discussion We show preserved optomotor response and ameliorated course of disease after anti-FcRn treatment in an experimental model using a monoclonal MOG-IgG to mimic MOGAD. Selectively targeting FcRn might represent a promising therapeutic approach in MOGAD.

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Applications:
Autoimmune Demyelinating Diseases
·
Experimental Autoimmune Encephalomyelitis
·
MOG Antibody-Associated Disorder
·
Multiple Sclerosis
·
Neuroinflammation and Autoimmune CNS Disease
·
Optic Neuritis
>

Nature Aging (Apr 15, 2021) Accumulation of cytotoxic T cells in the aged CNS leads to axon degeneration and contributes to cognitive and motor decline

Groh J, Knöpper K, Arampatzi P, Yuan X, Lößlein L, Saliba AE, Kastenmüller W, Martini R

DOI: 10.1038/s43587-021-00049-z >>

Journal Club

Featured image for “Accumulation of cytotoxic T cells in the aged CNS leads to axon degeneration and contributes to cognitive and motor decline”

Aging is often associated with damages and degeneration to the peripheral and central nervous system. Groh et al show that CD8+ T lymphocytes are causally involved in driving axon degeneration in the CNS in aging mice, a process that is further aggravated in aged mice by systemic inflammation. Functionally, these changes are also manifested in the visual system and Groh et al monitored them with our OptoDrum. Targeting such T cells may be a promising treatment against age-related decline of brain function.

Aging is a major risk factor for the development of nervous system functional decline, even in the absence of diseases or trauma. The axon–myelin units and synaptic terminals are some of the neural structures most vulnerable to aging-related deterioration, but the underlying mechanisms are poorly understood. In the peripheral nervous system, macrophages—important representatives of the innate immune system—are prominent drivers of structural and functional decline of myelinated fibers and motor endplates during aging. Similarly, in the aging central nervous system (CNS), microglial cells promote damage of myelinated axons and synapses. Here we examine the role of cytotoxic CD8+ T lymphocytes, a type of adaptive immune cells previously identified as amplifiers of axonal perturbation in various models of genetically mediated CNS diseases but understudied in the aging CNS. We show that accumulation of CD8+ T cells drives axon degeneration in the normal aging mouse CNS and contributes to age-related cognitive and motor decline. We characterize CD8+ T-cell population heterogeneity in the adult and aged mouse brain by single-cell transcriptomics and identify aging-related changes. Mechanistically, we provide evidence that CD8+ T cells drive axon degeneration in a T-cell receptor- and granzyme B-dependent manner. Cytotoxic neural damage is further aggravated by systemic inflammation in aged but not adult mice. We also find increased densities of T cells in white matter autopsy material from older humans. Our results suggest that targeting CD8+ CNS-associated T cells in older adults might mitigate aging-related decline of brain structure and function.

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Applications:
Aging
·
Autoimmune Demyelinating Diseases
·
Axon Degeneration
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Neuroinflammation
·
Neuroinflammation and Autoimmune CNS Disease
·
Ocular Inflammation and Immune-Mediated Eye Disease
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Systemic Aging and CNS decline
>

The Journal of Immunology (Apr 12, 2021) Conditional Deletions of Hdc Confirm Roles of Histamine in Anaphylaxis and Circadian Activity but Not in Autoimmune Encephalomyelitis

Morin F, Singh N, Mdzomba JB, Dumas A, Patenaude A, Pernet V, Vallières L

DOI: 10.4049/jimmunol.2000719 >>

Featured Publication

Featured image for “Role of Histamine in EAE | OptoDrum Paper”

Experimental autoimmune encephalomyelitis (EAE) is the most widely used animal model for multiple sclerosis (MS), an autoimmune disease where the immune system attacks myelin, which coats neurons in the CNS. Histamine has been thought to play a role in MS, effecting disease progression either positively or negatively, depending on the location of histamine action. In this study, Morin et al created a conditional mouse KO model of Hdc, the enzyme that synthesizes histamine, and induced EAE in these mice. Surprisingly, while some phenotypes in these mice were consistent with the lack of histamine, it had no impact on the development and severity of EAE. One behavioral readout of the disease progression in EAE is the decline of visual acuity, which can be measured with our OptoDrum. Consistent with the other observation, visual acuity declined in EAE Hdc-KO animals in the same way as in EAE Hdc-WT animals.

Histamine is best known for its role in allergies, but it could also be involved in autoimmune diseases such as multiple sclerosis. However, studies using experimental autoimmune encephalomyelitis (EAE), the most widely used animal model for multiple sclerosis, have reported conflicting observations and suggest the implication of a nonclassical source of histamine. In this study, we demonstrate that neutrophils are the main producers of histamine in the spinal cord of EAE mice. To assess the role of histamine by taking into account its different cellular sources, we used CRISPR-Cas9 to generate conditional knockout mice for the histamine-synthesizing enzyme histidine decarboxylase. We found that ubiquitous and cell-specific deletions do not affect the course of EAE. However, neutrophil-specific deletion attenuates hypothermia caused by IgE-mediated anaphylaxis, whereas neuron-specific deletion reduces circadian activity. In summary, this study refutes the role of histamine in EAE, unveils a role for neutrophil-derived histamine in IgE-mediated anaphylaxis, and establishes a new mouse model to re-explore the inflammatory and neurologic roles of histamine.

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