Research Applications for Striatech Products

Experimental Autoimmune Encephalomyelitis (EAE): Model Variants, Visual Endpoints, and Translational Benchmarking

EAE is the principal rodent paradigm for multiple sclerosis. Model variants (MOG, PLP, B-cell-dependent, passive transfer) differ in disease course and visual phenotype, with optic neuritis as a near-universal feature.

Introduction

Animal Models

Research Questions

Measurement Modalities

Publications

Journal Clubs

Introduction

What is Experimental Autoimmune Encephalomyelitis (EAE)?

Experimental autoimmune encephalomyelitis (EAE) is the most widely used preclinical model system for multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and MOG-antibody-associated disorder (MOGAD). Unlike the disease entities themselves, EAE is an induction-defined model: disease is triggered by active immunisation with myelin-derived peptides (such as MOG_35-55 or PLP_139-151) or by passive transfer of pathogenic antibodies (MOG-IgG, AQP4-IgG), with the variant chosen to match the research question: T cell-driven demyelination, B cell/antibody-mediated pathology, relapsing-remitting course, or primary progressive disease. Each variant produces a distinct pathological signature in the spinal cord, brain, and optic nerve, with correspondingly distinct visual functional consequences measurable by automated optomotor testing.

This page focuses specifically on EAE as a model system, including variant selection, induction protocols, visual endpoint timing, immunological mechanisms, and translational benchmarking applications. For the corresponding clinical context, see Multiple Sclerosis and Autoimmune Demyelinating Diseases.

The model is closely associated with Optic Neuritis as a key optic nerve and retinal consequence. It also links mechanistically to both Neuroinflammation and Autoimmune CNS Disease and Ocular Inflammation and Immune-Mediated Eye Disease, which addresses the ocular-specific consequences of systemic and CNS autoimmune processes.

Vision: A Window into the brain

Why Vision? EAE as a CNS Model with Ocular Consequences

EAE researchers who do not primarily study the visual system may ask why visual endpoints are relevant to their work. The answer is structural: the retina is CNS tissue, the optic nerve is a CNS white matter tract, and both are affected in the majority of EAE variants. Optic neuritis – inflammatory demyelination of the optic nerve – is a cardinal feature of MS in humans and occurs in most EAE models to varying degrees. RGC loss and axon degeneration in the optic nerve follow the inflammatory phase and provide a quantifiable structural record of cumulative damage.

Functionally, the optomotor reflex (OMR) is a subcortical reflex mediated by the accessory optic system and nucleus of the optic tract that captures the integrated output of retinal circuitry and optic nerve conduction. Because the OMR requires no training, anaesthesia, or surgical preparation, it can be measured repeatedly across the full EAE time course – from before immunisation through peak disease and into the chronic or remitting phase – in the same animals used for motor scoring. This temporal pairing of visual and motor endpoints in the same cohort substantially increases statistical power and reduces animal numbers (3Rs). For researchers benchmarking disease-modifying therapies, the OMR provides a non-invasive, sensitive functional readout that is directly analogous to the visual evoked potential (VEP) and optotype acuity endpoints used in MS clinical trials.

Animal Models

Common EAE Model Variants Used for Visual Endpoint Research

MOG_35-55 EAE (C57BL/6 mouse): The most widely replicated EAE variant. Subcutaneous immunisation with MOG peptide 35-55 emulsified in complete Freund's adjuvant (CFA) with pertussis toxin co-injection produces ascending paralysis peaking around day 14-21 post-immunisation, with spinal cord and optic nerve demyelination. Visual acuity and contrast sensitivity decline is detectable by OptoDrum from peak motor disease through the chronic phase, reflecting optic nerve demyelination and progressive RGC loss. The monophasic course in C57BL/6 mice supports clean single-episode intervention studies. (Capper et al., 2025, Front Immunol. | Morin et al., 2021, J Immunol. )
B cell-dependent EAE with anti-MOG antibody responses (C57BL/6 or humanised variants): Immunisation protocols incorporating anti-MOG antibodies or B cell- stimulating adjuvants produce a humoral immune component alongside T cell-driven inflammation, more closely recapitulating MOGAD pathology. Complement-mediated demyelination and a distinct optic neuritis profile distinguish this variant from canonical T cell-driven EAE, and OptoDrum captures the corresponding differences in functional visual trajectory. (Joly et al., 2022, J Neuroinflammation.)
MOGAD and NMOSD models (MOG-IgG and AQP4-IgG passive transfer): Passive transfer of human MOG-IgG or AQP4-IgG into rodents with an adjuvant optic nerve inflammatory trigger produces a severe, rapidly evolving optic neuritis that is distinct from EAE in its severity and the poor visual recovery that follows. OptoDrum has been used to document the functional visual phenotype of these disease-specific variants, establishing a benchmark against which disease-modifying therapies for NMOSD and MOGAD can be tested. (Remlinger et al., 2023, Neurol Neuroimmunol Neuroinflamm. | Remlinger et al., 2022, Neurol Neuroimmunol Neuroinflamm.)
Conditional immune gene knockout EAE (C57BL/6; histamine signalling knockouts): Cell-specific conditional deletion of histidine decarboxylase (Hdc) in different immune compartments creates mechanistically refined EAE variants for dissecting the role of specific immune mediators. OptoDrum quantifies the functional visual consequences of these genetic immunological manipulations with sufficient sensitivity to detect between-genotype differences in visual outcome. (Morin et al., 2021, J. Immunol.)
Dietary and environmental modulation of MOG_35-55 EAE (C57BL/6): High-saturated, long-chain fatty acid dietary regimens exacerbate EAE severity and visual pathway damage without altering the induction protocol. This variant demonstrates that environmental variables measurably shift OptoDrum-quantifiable visual outcomes, making it particularly relevant for studies examining diet-microbiome-neuroinflammation interactions in MS-relevant models. (Capper et al., 2025, Front. Immunol.)

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.

Which EAE Variant Best Models MS vs NMOSD vs MOGAD, and How Does the Visual Phenotype Differ?

Audience A - Vision-focused

Audience B - CNS/Systemic

Quick Answer

MOG_35-55/C57BL/6 EAE models T cell-driven MS with a monophasic visual acuity decline that partially recovers in some animals
PLP_139-151/ SJL/J EAE produces relapsing-remitting optic neuritis best captured by longitudinal OptoDrum tracking
B cell-dependent and MOG-IgG/AQP4-IgG passive transfer models produce the more severe, less remitting optic neuritis of MOGAD/NMOSD, with an OptoDrum functional profile that is diagnostically distinguishable from T cell-driven EAE

The challenge

MS, NMOSD, and MOGAD are distinct diseases with different pathological substrates, clinical courses, and treatment responses. Preclinical researchers need to select the EAE variant that best recapitulates the disease mechanism under investigation – T cell-mediated demyelination, astrocytopathy driven by AQP4-IgG, or complement-mediated axon attack driven by MOG-IgG – and then confirm that the chosen variant produces the expected visual phenotype. Mismatched model selection is a leading cause of failed translational predictions.

Classical motor scoring (Expanded Disability Status Scale analogues) does not disambiguate between these variants because all produce ascending paralysis. The visual pathway provides a complementary readout that more directly reflects optic nerve involvement, which varies markedly between variants. AQP4-IgG NMOSD models, for example, produce catastrophic optic nerve destruction with near-total OMR loss and minimal recovery, whereas T cell-driven EAE produces a partial, fluctuating deficit. Capturing this distinction non-invasively and longitudinally requires an endpoint that is repeatable across weeks without sacrifice.

Also see: Multiple Sclerosis, Autoimmune Demyelinating Diseases and Axon Degeneration.

How Striatech products help

OptoDrum

Measures spatial visual acuity (cycles per degree) and contrast sensitivity via the subcortical optomotor reflex in awake, unrestrained mice. In EAE variant comparison studies, it provides the functional visual phenotype – onset timing, nadir severity, recovery trajectory – that distinguishes T cell-driven, B cell-driven, and antibody-mediated disease variants without sacrifice.

AcuiSee

Measures visual acuity via an operant paradigm requiring cortical visual processing. Useful for assessing cortical visual pathway involvement in EAE variants where suprathreshold or higher-order visual function is of interest, complementing the retina-to-brainstem endpoint measured by OptoDrum.

Non-aversive Animal Platform

Provides restraint-free animal placement, reducing handling stress during OMR testing. Particularly relevant for EAE animals at peak disease where conventional restraint would be inappropriate for debilitated animals with motor deficits.

Evidence from the Literature

Remlinger et al (2023) Neurol. Neuroimmunol. Neuroinflamm.
Feature →
Remlinger et al (2023) Neurol. Neuroimmunol. Neuroinflamm.
Feature →
Developed and characterised rodent models for NMOSD and MOGAD using OptoDrum to document the distinct pattern of visual pathway dysfunction produced by AQP4-IgG and MOG-IgG-mediated attack. The functional visual profile was demonstrably different from classical T cell-driven EAE, establishing OptoDrum as the discriminating endpoint between autoimmune demyelinating disease models.
Joly et al (2022) J. Neuroinflammation
Characterised a B cell-dependent EAE variant in which MOG antibody responses drive demyelination alongside T cell-mediated inflammation. OptoDrum documented the functional visual consequence of this antibody-mediated optic nerve attack, providing evidence that the B cell/MOG-IgG arm of EAE produces a visual dysfunction profile distinct from canonical CD4+ T cell-driven disease.

When Do EAE Visual Deficits Emerge Relative to Motor Scoring, and Can OMR Testing Precede or Supplement the Clinical EAE Score?

Audience A - Vision-focused

Audience B - CNS/Systemic

Quick Answer

In MOG_35-55 C57BL/6 EAE, optomotor acuity and contrast sensitivity decline is detectable at or around the onset of motor symptoms, and persists through the chronic phase even after partial motor recovery. Repeated non-invasive OMR testing with OptoDrum can run in parallel with daily motor scoring in the same animals, adding a continuous visual function dimension to the standard EAE clinical timeline without additional cohorts or surgical intervention.

The challenge

The standard EAE clinical score (0-5 ascending paralysis scale) captures motor output but provides no information about cranial nerve involvement, optic neuritis severity, or the functional status of the retino-brainstem visual pathway. Motor score and visual function are partially dissociated: an animal scoring 2-3 on the motor scale may have near-normal vision or severe optic neuritis depending on the optic nerve involvement in that individual, which varies even within inbred strains.

Researchers optimising treatment windows need to know whether visual deficits precede, coincide with, or lag behind motor symptom onset. If visual deficits emerge early – potentially reflecting subclinical optic nerve inflammation before motor paralysis – OMR testing could serve as an early warning endpoint. If they persist after motor recovery, they capture the residual neurological damage most relevant to chronic disease staging. Both dynamics have direct translational relevance to clinical VEP prolongation in MS.

Conventionally, characterising the visual phenotype required ERG or histological RGC counts, both of which are terminal or require anaesthesia and provide only a single time point per animal. Repeated longitudinal visual function testing in the same EAE cohort, without anaesthesia or surgery, was not practically achievable before automated OMR platforms.

Also see: Neuroinflammation

How Striatech products help

OptoDrum

Measures visual acuity (cycles per degree) and contrast sensitivity via the optomotor reflex in awake, freely moving mice. Tests can be run in minutes without anaesthesia or training, enabling weekly or bi-weekly assessments across the full EAE time course – before immunisation (baseline), at onset, at peak, during partial recovery, and in the chronic phase. Temporal pairing of OMR and motor score in the same animal enables within-animal correlations between CNS visual and motor outcomes.

DarkAdapt

Provides controlled dark adaptation for scotopic OMR testing with the ScotopicKit extension. In EAE studies incorporating night-vision or rod pathway endpoints, DarkAdapt ensures consistent pre-adaptation conditions across all animals and time points.

Non-aversive Animal Platform

Eliminates restraint-induced stress during OMR testing, which is critical for EAE animals at peak disease where handling stress confounds motor and potentially autonomic readouts. Also appropriate for aged-onset EAE or progressive disease models where animals are chronically debilitated.

Evidence from the Literature

Remlinger et al (2023) Neurol. Neuroimmunol. Neuroinflamm.
Feature →
Capper et al (2025) Front Immunol.
Demonstrated that dietary fat composition measurably shifts visual function outcomes in EAE, with OptoDrum detecting between-group differences in visual acuity and contrast sensitivity at multiple time points across the disease course. The study validates OptoDrum sensitivity to environmental modulators of EAE severity, confirming that even moderate disease-course changes are captured functionally.
Morin et al (2021) J. Immunol.
Feature →
Used conditional Hdc knockouts to demonstrate that histaminergic immune modulation alters EAE severity and visual pathway functional outcomes. OptoDrum measured the functional visual consequences of these cell-specific immune manipulations, establishing that neuroimmune mediator changes produce OMR-detectable differences in visual function.

B Cell vs T Cell EAE: What Are the Distinct Immunological Mechanisms and Visual Signatures?

Audience A - Vision-focused

Audience B - CNS/Systemic

Quick Answer

Classical MOG_35-55 EAE is driven by CD4+ T helper 17 and T helper 1 cells that orchestrate demyelination via microglia and macrophage activation. B cell-dependent EAE additionally incorporates MOG-specific antibodies that engage complement- mediated lysis of myelin and oligodendrocytes, producing a distinct optic neuritis profile with potentially greater axon loss and a visual dysfunction trajectory that OptoDrum can differentiate from the T cell-only model. This distinction is critical for benchmarking B cell-targeting therapies such as anti-CD20 agents.

The challenge

MS treatment has been transformed by anti-CD20 therapies (ocrelizumab, ofatumumab) that deplete B cells, reducing relapse rates in both relapsing-remitting and primary progressive MS. Yet the standard EAE model used in most preclinical laboratories is a T cell-driven model that lacks the humoral immune component. Preclinical evaluation of B cell-targeted therapies in a B cell- dependent EAE model with a validated visual endpoint would provide a more mechanistically faithful translational platform.

B cells contribute to MS and MOGAD pathology through several non-redundant mechanisms: as antigen-presenting cells that license autoreactive T cells, as producers of MOG-specific and AQP4- specific antibodies that engage complement at the node of Ranvier and at astrocytic endfeet, and as sources of pro-inflammatory cytokines (GM-CSF, IL-6) that amplify local inflammation. Each mechanism has a different downstream effect on the optic nerve and retina, and the functional visual trajectory differs accordingly. Without a validated functional endpoint, researchers cannot determine whether a B cell-targeting intervention is reducing the T cell licensing arm, the antibody-mediated arm, or both.

Also see: Optic Nerve Damage, Retinal Ganglion Cell Pathology and Optic Neuritis.

How Striatech products help

OptoDrum

Provides the functional visual endpoint for comparing B cell-dependent and T cell-driven EAE variants in the same experiment or across cohorts. The OMR captures the integrated output of the optic nerve-retina axis; a more severe or sustained OMR deficit in the B cell/antibody model compared to the T cell model provides functional evidence that humoral mechanisms add a distinct layer of visual pathway damage beyond T cell-driven demyelination alone.

AcuiSee

Measures cortical visual acuity via operant testing. Where B cell-dependent EAE produces more severe optic nerve damage with associated visual cortex reorganisation, AcuiSee can provide the cortical-level complement to OptoDrum's subcortical OMR measurement.

Evidence from the Literature

Remlinger et al (2023) Neurol. Neuroimmunol. Neuroinflamm.
Feature →
Joly et al (2022) J. Neuroinflammation
Characterised a B cell-dependent EAE model incorporating MOG-specific antibody responses. OptoDrum measured visual acuity and contrast sensitivity to document that B cell/antibody-driven EAE produces optic neuritis and RGC death with a functional visual profile distinguishable from classical CD4+ T cell-driven disease. The study establishes a functional visual benchmark for evaluating B cell-targeted therapies – including anti-CD20 monoclonals – in this model.

Disease-Modifying Therapy Benchmarking in EAE Using Visual Endpoints: What Can OptoDrum Detect?

Audience A - Vision-focused

Quick Answer

OptoDrum provides a sensitive, non-invasive functional endpoint for benchmarking disease-modifying therapies (DMTs) in EAE, including neuroprotective agents (HIF-1 inhibitors), antibody-clearing therapies (FcRn blockade), and immunomodulatory compounds. Published studies demonstrate that pharmacological interventions that preserve optic nerve integrity produce statistically discriminable improvements in OptoDrum-measured visual acuity and contrast sensitivity relative to vehicle-treated controls.

The challenge

Motor scoring is the standard readout for EAE therapy studies, but it has well-documented limitations as a translational endpoint: it is categorical, subject to inter-rater variability, and does not map cleanly onto the patient-relevant outcomes used in MS clinical trials (such as relapse rate, VEP latency, optical coherence tomography retinal nerve fibre layer thickness, or Expanded Disability Status Scale). The visual pathway provides a set of endpoints – functional acuity, contrast sensitivity, optic nerve conduction – that more directly parallel the clinical outcome measures used in MS trials, strengthening the translational argument for preclinical efficacy data.

Beyond the translational alignment argument, visual endpoints offer a practical advantage: they are continuously measurable in the same animals used for motor scoring, without adding cohorts or terminal procedures. This allows researchers to establish an intervention's functional efficacy profile across the full treatment window – whether a compound prevents the initial deficit, promotes recovery during remission, or slows progression in the chronic phase – rather than capturing only a single post-treatment time point at sacrifice.

Also see: Retinal Ganglion Cell Pathology

How Striatech products help

OptoDrum

Measures visual acuity and contrast sensitivity as the primary functional readout for DMT efficacy in EAE. Because the OMR is non-invasive and rapid (3-5 minutes per animal), it can be run at every time point planned for motor scoring, yielding a continuous functional visual curve against which the treatment effect can be quantified. Treatment-preserved visual acuity provides a functional correlate of optic nerve integrity that complements histological RGC counts and is directly analogous to clinical VEP measurements.

AcuiSee

Assesses cortical visual acuity via operant visual discrimination. For DMT studies where suprathreshold visual processing or cortical visual pathway outcomes are of interest – particularly relevant for MS models where cortical grey matter lesions contribute to cognitive and visual impairment – AcuiSee provides the cortical complement to OptoDrum's subcortical OMR endpoint.

Non-aversive Animal Platform

Minimises handling stress during repeated OMR testing in treated EAE cohorts, particularly important for chronically treated animals where stress-corticosteroid interactions could confound immunological outcomes and visual function measurements.

Evidence from the Literature

Remlinger et al (2023) Neurol. Neuroimmunol. Neuroinflamm.
Feature →
Anders et al (2023) Front Immunol.
Demonstrated that pharmacological inhibition of HIF-1 (hypoxia-inducible factor 1) with acriflavine preserves visual function in EAE by reducing optic nerve hypoxia-driven neuroinflammation. OptoDrum provided the primary functional efficacy endpoint, confirming that HIF-1 inhibition translates to retained optomotor visual acuity and reduced optic neuritis severity. This study represents a mechanistically novel DMT approach – targeting the metabolic-inflammatory interface rather than conventional immune cell depletion – validated with a visual function endpoint.
Remlinger et al (2022) Neurol. Neuroimmunol. Neuroinflamm.
Journal Club →
Evaluated FcRn receptor blockade as a strategy to reduce circulating MOG antibody titres and attenuate EAE/MOGAD-related optic neuritis. FcRn blockade is a clinically advanced therapeutic strategy already in use for other antibody-driven diseases (myasthenia gravis, NMOSD). OptoDrum measured visual acuity as the functional confirmation that antibody reduction via FcRn blockade translates to preserved visual pathway integrity.

Chronic Progressive vs Relapsing EAE: How Do OMR Longitudinal Trajectories Differ, and What Does This Mean for Endpoint Planning?

Audience A - Vision-focused

Audience B - CNS/Systemic

Quick Answer

Relapsing EAE variants (PLP_139-151/SJL/J) produce episodic optomotor acuity loss aligned with relapses, with partial inter-episode recovery; chronic progressive variants (MOG_35-55/C57BL/6 in aged or persistently immunised settings, or NMOSD passive transfer models) produce a sustained, non-recovering OMR deficit. Distinguishing these trajectories with OptoDrum enables researchers to set appropriate sampling intervals, power calculations, and intervention timing for each disease model type.

The challenge

Endpoint planning for EAE therapy studies requires knowledge of the expected visual function trajectory for the chosen model variant. A compound evaluated in a relapsing model must be sampled frequently enough to capture peak deficit during relapses and partial recovery between attacks; a compound evaluated in a chronic progressive model must be sampled over a long enough window to detect rate-of-decline differences between treatment groups. Using the wrong sampling frequency or study duration for the disease course produces underpowered studies with inconclusive functional endpoints.

The relapsing-remitting vs chronic progressive distinction also maps differently onto clinical endpoints. Relapsing EAE visual function data most directly parallels the episodic VEP changes seen during MS clinical relapses, while chronic progressive EAE OMR trajectories better model the progressive retinal nerve fibre layer thinning and sustained VEP latency prolongation seen in secondary progressive MS and NMOSD. Aligning the preclinical endpoint strategy with the clinical measurement precedent strengthens the translational argument for regulatory submissions.

Also see: Neuroinflammation and Optic Nerve Damage

How Striatech products help

OptoDrum

Enables weekly or bi-weekly non-invasive OMR assessments across the full EAE study duration. In relapsing models, this captures the full relapse-remission visual cycle in the same animals; in chronic progressive models, it provides a continuous visual decline curve against which treatment-induced rate-of-decline differences can be detected. The non-invasive format means sampling density is limited only by study design, not by animal welfare constraints.

DarkAdapt

Enables scotopic OMR testing (with the ScotopicKit extension) to assess rod-pathway visual function as a complement to photopic acuity measurements. In EAE models with outer retinal involvement or studies incorporating circadian rhythm analysis, controlled dark adaptation via DarkAdapt ensures reproducible scotopic baseline conditions.

Non-aversive Animal Platform

Particularly important for chronic studies and aged EAE animals where stress responses may differ across disease stages. Restraint-free testing maintains consistent test conditions across the longitudinal study, reducing stress-related variability in repeated-measures designs.

Evidence from the Literature

Remlinger et al (2023) Neurol. Neuroimmunol. Neuroinflamm.
Feature →
Capper et al (2025) Front Immunol.
Establishes the longitudinal optomotor endpoint profile, measured with OptoDrum, across multiple EAE variants.
Morin et al (2021) J. Immunol.
Feature →
Longitudinal OMR data (using OptoDrum) in MOG_35-55/C57BL/6 EAE is provided under different modulating conditions (dietary and immunological), establishing the expected deficit trajectory and its sensitivity to between-group differences.
Remlinger et al (2023) Neurol. Neuroimmunol. Neuroinflamm.
Feature →
Documents the more severe and persistent OMR trajectory (measured with OptoDrum) of NMOSD/MOGAD passive transfer variants, providing the comparative benchmark for chronic non-remitting disease modelling.

Product Fit

Summary: Striatech Products supporting your research questions

Research Question	OptoDrum	ScotopicKit	AcuiSee	DarkAdapt	Non-aversive platform
Variant selection (MS vs NMOSD vs MOGAD)	Yes		Yes		Yes
Visual onset timing vs motor score	Yes	Yes		Yes	Yes
B cell vs T cell mechanisms	Yes		Yes		Yes
DMT benchmarking	Yes		Yes		Yes
Longitudinal trajectories	Yes	Yes		Yes	Yes

Measurement Modalities

Measuring Functional Visual Outcomes in Experimental Autoimmune Encephalomyelitis (EAE): How Do Available Methods Compare?

Modality	Invasiveness	Repeatable longitudinally	Training required	Automation	Endpoint type	Translational analogue
OptoDrum (OMR)	None	Yes – weekly or more frequent	None	Fully automated	Subcortical functional acuity and contrast sensitivity	VEP acuity component; psychophysical optotype acuity
AcuiSee (operant)	None	Yes	Operant shaping (days to weeks)	Automated reward delivery	Cortical visual acuity	Clinical optotype visual acuity (ETDRS)
VEP (flash or pattern)	Requires anaesthesia or chronic electrode implant	Limited by anaesthesia / electrode welfare	Moderate (electrode preparation)	Semi-automated	Cortical evoked potential; latency and amplitude	Clinical VEP (direct equivalent)
ERG	Requires anaesthesia	Limited by anaesthesia	Moderate	Semi-automated	Retinal photoreceptor and inner nuclear layer function	Clinical full-field ERG
RGC histology / OCT	Terminal (histology); non-invasive (OCT)	OCT: yes; histology: no	High (histology); moderate (OCT)	Semi-automated (OCT)	Structural cell count / layer thickness	Clinical OCT retinal nerve fibre layer
Motor EAE score	None (observation)	Yes – daily	None	Not automated (observer-rated)	Motor disability	EDSS (partial analogue)

Note: OptoDrum measures the subcortical optomotor reflex, not cortical visual processing. Where cortical visual pathway involvement is the primary question, AcuiSee (operant visual discrimination requiring cortical processing) or VEP recording provides the appropriate cortical endpoint. The two modalities are complementary: OptoDrum provides the retina-to-brainstem functional readout, AcuiSee provides the perceptual/cortical readout.

Supported by Striatech Products

Publications on Experimental Autoimmune Encephalomyelitis (EAE)

Frontiers in Immunology (May 22, 2025) A high-saturated, long-chain fatty acid ketogenic diet negatively impacts visual and motor-sensory function in a pre-clinical model of multiple sclerosis

Capper EN, Anders JJ, Elwood BW, Kardon RH, Gramlich OW

DOI: 10.3389/fimmu.2025.1587760 >>

Featured image for “A high-saturated, long-chain fatty acid ketogenic diet negatively impacts visual and motor-sensory function in a pre-clinical model of multiple sclerosis”

Capper et al. investigated whether a ketogenic diet (KD) composed of long-chain saturated fatty acids provides neuroprotection in an EAE mouse model. Across preconditioned, prophylactic, and late KD interventions, the diet did not improve visual outcomes, and early KD even modestly worsened motor-sensory and visual deficits, without affecting optic nerve damage or retinal ganglion cell loss. The authors conclude that the neuroprotective potential of KD is limited when long-chain saturated fats are used. OptoDrum was used to assess bilateral visual acuity in each mouse.

Introduction: Multiple sclerosis (MS) is a neurodegenerative condition that results in demyelination of the central nervous system. Visual impairment, retinal nerve fiber layer thinning, and impaired electrical function in retinal ganglion cells are seen throughout disease progression and serve as useful markers for treatment success. Current research examining the effects of ketogenic diet (KD) as cotherapy show promising anti-inflammatory properties, but research remains limited by differences in experimental set-up and KD composition. The purpose of our study was to use functional and structural biomarkers to determine the neuroprotective effects of a KD composed of long-chain, saturated fatty acids and how the timing of its implementation impacts these biomarkers in an experimental autoimmune encephalomyelitis (EAE) model. Methods: EAE was induced in 80 female C57BL/6J mice by immunization with MOG35-55 and randomly assigned to stay on the standard diet or to start the KD at one of three time points (preconditioned, prophylactic, or late). Motor-sensory scores, visual acuity, OCT, electrophysiology, and histopathology were performed. Results: In general, our results show that a KD with long-chain, saturated fatty acids did not significantly improve visual outcomes, and that early implementation of the diet modestly exacerbated motor-sensory and visual acuity deficits despite not impacting optic nerve axonal damage, retinal ganglion cell loss, or psychomotor measurements of visual system function. Discussion: We propose that the anti-inflammatory neuroprotective benefits of a KD are limited when saturated, long-chain fatty acids are used, and that chain length and fat saturation should be taken into account when utilizing KD as a treatment.

Keywords: EAE; RGC; electrophysiology; fatty acids; ketogenic diet; multiple sclerosis; optic neuritis; saturated fats.

Related Products:

OptoDrum

Applications:
Experimental Autoimmune Encephalomyelitis (EAE)
·
Multiple Sclerosis
·
Neuroinflammation
·
Neuroinflammation and Autoimmune CNS Disease
·
Ocular Inflammation and Immune-Mediated Eye Disease
·
Optic Nerve Damage
·
Optic Neuritis
·
Retinal Ganglion Cell Pathology
>

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

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 Publication

Featured image for “Characterizing Visual Manifestations in NMOSD and MOGAD Mouse Models”

This study evaluated whether antibody-driven mouse models of neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) reproduce the distinct visual outcomes observed in patients. Researchers induced experimental autoimmune encephalomyelitis and administered disease-specific antibodies before assessing visual acuity, retinal structure, and optic nerve pathology over time. Both models developed similar visual impairment and retinal degeneration, despite subtle histological differences in optic nerve inflammation. Visual acuity was measured using the OptoDrum to monitor disease progression.

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
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Experimental Autoimmune Encephalomyelitis (EAE)
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MOG Antibody-Associated Disorder
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Multiple Sclerosis
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Neuroinflammation and Autoimmune CNS Disease
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Optic Neuritis
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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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