Research Applications for Striatech Products

Rare Disease

Individually uncommon, collectively affecting 300 million people — and uniquely tractable in preclinical research because the causal molecular lesion is known. The visual system is often a primary target or an early indicator of CNS pathology.
Introduction

What is Rare Disease?

Rare diseases are individually uncommon but collectively numerous, affecting an estimated 300 million people worldwide. Many rare disorders – including lysosomal storage diseases, inherited leukodystrophies, rare autoinflammatory syndromes, and mitochondrial enzyme deficiencies – involve the visual system as either a primary target or an early indicator of CNS pathology. Because rare diseases typically arise from single well-characterised gene variants, their animal models offer a degree of mechanistic precision that is difficult to achieve in polygenic or acquired-disease models: the causal molecular lesion is known, its downstream pathology is predictable, and the functional consequences can be tracked longitudinally without ambiguity about the underlying driver. This mechanistic tractability makes rare-disease models uniquely powerful tools for dissecting fundamental biology, validating functional endpoints, and testing mechanism-targeted therapies. This page focuses on the cross-cutting mechanistic and methodological threads that connect rare-disease preclinical research – how single-gene models provide biological tractability for mechanism dissection, how functional visual readouts serve as non-invasive biomarkers in natural-history studies, how neuroinflammation acts as a pathomechanism amplifier in inherited disorders, and how rare metabolic deficiencies are detected through visual system consequences. These themes span multiple disease areas: Rare and Inherited CNS and Eye Disorders, Retinal Degeneration and Inherited Retinal Disease (photoreceptor and RPE disease context), Glaucoma and Optic Nerve Neurodegeneration (optic nerve and RGC degeneration), Neuroinflammation and Autoimmune CNS Disease, Ocular Inflammation and Immune-Mediated Eye Disease, Neurodevelopment and Circuit Mechanisms, Ocular and CNS Toxicity Models, Maintaining and Restoring Vision.
Vision: A Window into the brain 

Why Are Visual Endpoints Relevant in Rare Disease Research?

Several rare diseases covered in the publication evidence base are not primarily ocular disorders: Wolfram syndrome is defined by diabetes insipidus, diabetes mellitus, optic atrophy, and deafness (DIDMOAD); Allan-Herndon-Dudley syndrome is a severe CNS hypomyelination disorder; hereditary spastic paraplegia affects corticospinal tract axons; neuronal ceroid lipofuscinoses cause progressive CNS degeneration. In each case, the visual system provides a non-invasive window into CNS pathology. The retina is CNS tissue, sharing developmental origin, myelination biology, and metabolic requirements with the brain; the optic nerve is a central white matter tract. Progressive visual decline in these conditions reflects the same molecular and cellular mechanisms – metabolic failure, neuroinflammation, axon degeneration, lysosomal dysfunction – that drive CNS pathology more broadly. For researchers working on any of these rare disorders, functional visual readouts measured by automated optomotor or operant acuity testing provide a non-invasive, repeatable endpoint that can substitute for, or complement, terminal histological sampling at multiple disease stages. This is particularly valuable when models exhibit severe motor impairment – such as in AHDS – that confounds conventional locomotor behavioural assays.
Animal Models

What Are Common Animal Models For Rare Disease?

The following models appear directly in the rare-disease cluster publication evidence base and have confirmed rare-disease-specific studies using Striatech visual endpoints. For the full rare-disease model catalogue, including models studied on parent application areas, see Rare and Inherited CNS and Eye Disorders.
  • Jimpy mouse (Plp1jp/Y) – classical severe model of Pelizaeus-Merzbacher disease (PLP1 mutation producing CNS hypomyelination). Visual function is impaired and measurable by OptoDrum; among the earliest named rare-disease demonstrations of optomotor testing.
  • CLN1 / Ppt1-knockout mouse – infantile neuronal ceroid lipofuscinosis (NCL) model; progressive retinal and CNS degeneration driven by lysosomal dysfunction and neuroinflammation. Visual decline is staged and trackable longitudinally by OptoDrum.
  • Wfs1-mutant mouse – Wolfram syndrome model; progressive optic nerve degeneration driven by MCT1-mediated metabolic failure and secondary neuroinflammation. OptoDrum tracks visual acuity longitudinally alongside optic nerve structural endpoints.
  • Mct8/Oatp1c1 double-knockout mouse – Allan-Herndon-Dudley syndrome model; severe CNS hypomyelination due to thyroid hormone transporter deficiency. OptoDrum provides a CNS functional readout where motor confounders preclude standard locomotor assays.
  • Pnpla6 (NTE)-deficient mouse – model of Gordon Holmes syndrome / Oliver McFarlane syndrome; progressive optic nerve damage and retinal dystrophy. Visual decline measured by OptoDrum alongside histological optic nerve endpoints.
  • EP300 chromatin remodelling knock-in mouse (Sifrim-Hitz-Weiss syndrome) – constitutive and conditional allelic series; divergent visual circuit phenotypes discriminated by OptoDrum, directly informing model-design decisions for rare neurodevelopmental research.
  • ALPK1 gain-of-function mouse (ROSAH syndrome) – innate immune kinase mutation producing autoinflammatory ocular disease with retinal dystrophy and optic nerve oedema. OptoDrum measures functional visual response to ALPK1 inhibitor treatment.
  • Mitochondrial complex I-deficient mouse – genetic model of mitochondrial metabolic disease with progressive retinal degeneration; non-invasive ophthalmological battery including OptoDrum validated for longitudinal monitoring.
  • Inherited retinal degeneration models (e.g. rd or equivalent) – stage-dependent visual acuity and contrast sensitivity profiling used to define the functional therapeutic window; applicable to multiple inherited retinal dystrophy genotypes.
  • Rare inherited glaucoma models – candidate mouse models for rare inherited forms of glaucoma, evaluated by OptoDrum for quantitative functional discrimination between model phenotypes.
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.
01
How Do Single-Gene Rare Disease Models Provide Mechanistic Tractability That Multi-Gene Models Cannot, and What Role Does Visual Function Phenotyping Play?
Audience A - Vision-focused

Quick Answer

Single-gene rare disease models – such as Plp1-mutant (PMD), Pnpla6-deficient (Gordon Holmes syndrome), and EP300 knock-in (Sifrim-Hitz-Weiss syndrome) mice – allow researchers to attribute functional visual changes unambiguously to a defined molecular lesion. OptoDrum-measured spatial visual acuity provides the functional read-out that discriminates between model variants, validates genetic strategies, and quantifies the severity of circuit disruption without terminal tissue collection.

The challenge

A fundamental obstacle in rare disease research is knowing whether a given animal model faithfully recapitulates the human phenotype at the functional level. Histological and biochemical endpoints are informative but terminal, which limits the ability to perform longitudinal tracking within the same animals, particularly when cohort sizes are constrained by the rarity or cost of the model. Moreover, when two genetic strategies exist for modelling the same mutation – for example, constitutive versus conditional knock-in – there is no obvious way to determine which produces the more clinically relevant phenotype without a sensitive, functional discriminant.

Single-gene rare disease models offer a structural advantage over complex polygenic models: because the causal lesion is known, any functional abnormality can be attributed directly to the gene of interest rather than to unresolved genetic background effects. The visual circuit – accessible, anatomically discrete, and functionally testable without invasive procedures – provides an ideal endpoint for exploiting this tractability. Myelination-related rare diseases such as PMD affect the visual pathway predictably; lipid metabolism disorders such as PNPLA6 deficiency affect retinal and optic nerve integrity; neurodevelopmental chromatin-remodelling disorders alter circuit formation. In each case, a functional visual endpoint anchors the phenotypic characterisation in a biologically meaningful, clinically relevant outcome.

For a broader discussion of how neurodevelopmental mechanisms shape visual circuit function, see Neurodevelopment and Circuit Mechanisms. For optic nerve involvement in rare disorders, see also the focused discussion of axonopathy mechanisms in Optic Nerve Damage: Axonopathy, Functional Consequences, and Longitudinal Visual Readouts.

How Striatech products help

OptoDrum

Measures spatial visual acuity (cycles per degree) and contrast sensitivity threshold via the optomotor reflex in awake, freely moving mice. Provides a non-invasive, repeatable functional phenotypic discriminant between rare-disease model variants (e.g. constitutive vs. conditional knock-in strategies) and between genotypes within an allelic series.

AcuiSee

Measures visual acuity via a cortical operant discrimination paradigm, enabling assessment of suprathreshold visual perception and learned discrimination in rare neurodevelopmental models where cortical visual processing may be independently compromised.

Non-aversive Animal Platform

Provides a restraint-free testing surface that minimises handling stress, critical for rare-disease models with compromised motor function, debilitation, or unusual phenotypes that make conventional restraint stressful or impractical.

Evidence from the Literature

  • Kinuthia et al (2025) JCI Insight.
  • Hovhannisyan et al (2015) J. Comp. Neurol.

    Hovhannisyan et al – Used OptoDrum to characterise visual acuity impairment in jimpy mice (Plp1jp/Y), the classical severe model of Pelizaeus-Merzbacher disease. This 2015 study is among the earliest demonstrations that a named rare inherited CNS disease produces a quantifiable functional visual deficit measurable by the optomotor reflex, establishing that CNS myelin integrity is directly readable from the visual circuit. OptoDrum was confirmed as the measurement instrument (related-to-product-optodrum).

  • Larrigan et al (2023) Hum Mol Genet.

    Larrigan et al – Compared constitutive and conditional knock-in strategies for modelling Sifrim-Hitz-Weiss syndrome (EP300 mutation) and used OptoDrum to distinguish visual circuit phenotype severity between the two approaches. The study demonstrates that the method of genetic model construction – not only the gene itself – critically determines the functional phenotypic outcome, a finding with direct implications for rare-disease model validation. OptoDrum confirmed as the discriminant endpoint.

  • Liu et al (2024) Brain.

    Liu et al – Characterised progressive optic nerve damage, retinal dystrophy, and visual function decline in NTE/PNPLA6-deficient mice (Gordon Holmes syndrome / Oliver McFarlane syndrome model). OptoDrum measured visual acuity as the functional correlate of structural lipid-metabolism-dependent axon and photoreceptor degeneration, illustrating how single-gene lipid enzyme deficiencies affect the visual system in a predictable and measurable way. OptoDrum confirmed.

  • Eckhardt et al (2020) Hum. Mol. Genet.

    Eckhardt et al – Investigated the molecular basis of excitation-contraction coupling defects in a congenital myopathy model, using OptoDrum to assess optomotor function in a rare muscle disorder where extraocular and cervical muscle involvement can affect the motor component of the reflex arc. While the connection to visual acuity per se is indirect in this case, the study illustrates how OptoDrum can probe the integrity of the full OMR circuit – visual detection and motor execution – in rare neuromuscular disease contexts. Striatech instrument confirmed.

02
How Can Functional Visual Testing Define the Therapeutic Window and Serve as a Longitudinal Natural-History Biomarker in Rare Inherited Disorders?
Audience A - Vision-focused

Quick Answer

Functional visual testing with OptoDrum enables repeated, non-invasive tracking of disease progression within individual animals across multiple time points, defining when functional decline becomes irreversible and identifying the window in which a treatment must be initiated to achieve meaningful rescue. This approach has been validated in inherited retinal degeneration, Wolfram syndrome, CLN1 disease, and rare inherited glaucoma models.

The challenge

Natural-history studies in rare disease models face a fundamental tension between the need for longitudinal data and the terminal nature of most histological and electrophysiological endpoints. If a researcher must sacrifice animals at each time point to collect tissue, the cohort requirements rapidly exceed what rare-disease models – often expensive, slowly breeding, or genetically constrained – can support. At the same time, the therapeutic window in many rare diseases is narrow: intervention before a certain stage of degeneration may preserve function, while later intervention may be futile.

Functional visual endpoints measured by the optomotor reflex are uniquely suited to natural-history study design because they are non-invasive, require no surgical preparation, are completed in minutes per animal, and can be repeated in the same animal weekly or monthly without affecting subsequent measurements. This enables within-animal trajectory profiling, reducing cohort requirements and statistical noise simultaneously. It also allows researchers to identify the exact disease stage at which visual function becomes irreversible, directly informing the choice of treatment initiation time point in efficacy studies.

For discussion of stage-specific functional readouts in the context of retinal degeneration more broadly, see Retinal Degeneration Across Disease Contexts: Mechanistic Crosscutting Themes, Secondary Outcomes, and Functional Readouts. For model selection in rare inherited glaucoma, see also Glaucoma as a Cross-Context Preclinical Model.

How Striatech products help

OptoDrum

Provides repeated, non-invasive spatial visual acuity (cycles per degree) and contrast sensitivity measurements via the optomotor reflex. Enables within-animal longitudinal profiling across disease stages to define functional natural history and the therapeutic window.

ScotopicKit

Extends OptoDrum to scotopic (rod-mediated) visual acuity measurement after dark adaptation, enabling separate tracking of rod and cone pathway progression in inherited retinal dystrophies.

DarkAdapt

Provides a controlled, light-tight dark-adaptation environment for animals prior to scotopic OMR testing, ensuring consistent adaptation state across longitudinal measurement sessions.

Non-aversive Animal Platform

Reduces handling-related stress artefacts in repeated-measures longitudinal studies, ensuring that observed functional changes reflect disease progression rather than habituation or distress effects.

Evidence from the Literature

  • Kinuthia et al (2025) JCI Insight.
  • Cha et al (2022) Front. Cell. Neurosci.

    Cha et al – Characterised stage-dependent changes in spatial visual acuity and contrast sensitivity across the progression of inherited retinal degeneration, mapping the functional timeline from early photoreceptor loss through functional blindness. The study provides the empirical framework for identifying the therapeutic window – the stage range within which an intervention must be initiated to achieve functional rescue – and establishes OptoDrum-compatible endpoints as valid natural-history markers in inherited retinal dystrophy models. Striatech instrument confirmed.

  • Rossi et al (2023) Elife

    Rossi et al – Characterised the longitudinal functional visual trajectory in Wfs1-mutant mice (Wolfram syndrome model), using OptoDrum to track optic nerve degeneration non-invasively across disease stages. The metabolic (MCT1-dependent lactate transport) and neuroinflammatory mechanisms driving progressive optic neuropathy were dissected in parallel with the functional readout, demonstrating how OptoDrum can serve simultaneously as a natural-history biomarker and a mechanistic validation endpoint. Striatech instrument confirmed.

  • Groh et al (2021) Brain Commun.
    Journal Club →

    Groh et al – Used OptoDrum to track visual function longitudinally in CLN1 (Ppt1-/-) mice, providing a non-invasive functional biomarker of disease progression and treatment response across multiple time points. Immune modulation attenuated neurodegeneration, with visual function preservation serving as the primary functional endpoint confirming treatment efficacy. This study demonstrates the power of non-invasive longitudinal tracking in a rare lysosomal storage disorder where frequent terminal collection would be prohibitive. Striatech instrument confirmed.

  • Kuchtey et al (2024) Am J Ophthalmol.

    Kuchtey et al – Evaluated multiple candidate mouse models for rare inherited forms of glaucoma using OptoDrum visual acuity measurement as the discriminant for model phenotype fidelity. The study demonstrates that functional visual testing can resolve meaningful differences between candidate models at the behavioural level, enabling informed model selection before committing to large-scale long-term studies. This approach of using OMR-based functional testing as a model-selection tool is directly applicable to any rare disorder where multiple genetic strategies are under consideration. Striatech instrument confirmed.

03
How Does Neuroinflammation Function as a Pathomechanism Amplifier in Single-Gene Rare CNS Disorders, and Does It Produce Distinct Functional Visual Signatures?
Audience A - Vision-focused
Audience B - CNS/Systemic

Quick Answer

In several single-gene rare CNS disorders – including NCL/CLN1 disease, hereditary spastic paraplegia, and microglial-depletion models – neuroinflammation acts as a secondary amplifier of primary genetic pathology. OptoDrum-measured visual acuity documents the functional consequence of this amplification and can reveal sex-dimorphic and region-specific patterns that are invisible to purely structural endpoints.

The challenge

Neuroinflammation in rare disease is not simply an epiphenomenon: activated microglia, complement cascade engagement, and T-cell infiltration have been documented as active contributors to neurodegeneration in lysosomal storage disorders, leukodystrophies, and rare motor neuron diseases. However, distinguishing the functional visual consequences of the primary genetic defect from those of the superimposed neuroinflammatory component is technically demanding. Animal studies that use microglial depletion or anti-inflammatory treatment as a mechanistic tool can isolate the inflammatory contribution, but require a sensitive, non-invasive functional endpoint to reveal the downstream visual circuit consequence.

An additional complexity is sex dimorphism: microglial biology is increasingly recognised as sex-dependent, with female and male animals showing different microglial densities, activation states, and regional distributions. If visual functional readouts reveal sex-dimorphic consequences of microglial perturbation, this has direct implications for experimental design in rare-disease models – specifically, the need for sex-balanced cohorts and sex-stratified analysis when using visual endpoints.

For a comprehensive treatment of neuroinflammation as a primary topic including EAE, MS, and optic neuritis models, see Neuroinflammation and Autoimmune CNS Disease and the focused cross-context discussion at Neuroinflammation as a Driver of Visual System Dysfunction. The present section addresses specifically how neuroinflammation functions within the context of single-gene rare disorders, where it is a secondary amplifier rather than the primary disease driver.

How Striatech products help

OptoDrum

Measures spatial visual acuity via the subcortical optomotor reflex – a read-out of retino-recipient pathway integrity that is sensitive to both primary genetic pathology and secondary neuroinflammatory damage to the retina and optic nerve. Repeated testing within the same animals reveals the timeline of neuroinflammatory escalation as a functional deterioration gradient.

Non-aversive Animal Platform

Minimises stress-induced microglial activation that could confound interpretation of neuroinflammatory contributions in rare-disease models; particularly relevant for studies comparing microglial depletion vs. intact conditions.

Evidence from the Literature

  • Kinuthia et al (2025) JCI Insight.
  • Berve et al (2020) J. Neuroinflammation
    Feature →

    Berve et al – Investigated sex- and region-specific patterns of retinal microglial depletion and used OptoDrum to document the functional visual consequences of microglial loss and pharmacological modulation. The study revealed that the functional visual impact of microglial dynamics is sex-dimorphic – female and male animals show different functional responses to the same microglial perturbation. This result carries direct experimental design implications for any rare-disease study using visual endpoints: sex-balanced cohort design and sex-stratified analysis are necessary to avoid masking or artificially inflating treatment effects. OptoDrum confirmed as the functional endpoint.

  • Hörner et al (2024) Thesis

    Horner et al – Investigated the neuroinflammatory component of hereditary spastic paraplegia models, examining whether inflammation contributes to axon degeneration and associated visual pathway dysfunction. OptoDrum documented visual acuity changes associated with HSP-related neuroinflammation, establishing the visual endpoint as a readout of axonopathic severity in a rare inherited motor neuron disease. The study exemplifies how neuroinflammation can amplify the functional consequences of a primary genetic axonopathy, and how visual endpoints can capture this amplification non-invasively. Striatech instrument confirmed.

  • For context on how immune modulation translates to preserved functional vision in a rare NCL disorder – where neuroinflammation is a principal driver rather than a secondary amplifier – see Groh et al (2021) in the natural-history section above, and for the broader neuroinflammation-rare disease interface see Ocular Inflammation and Immune-Mediated Eye Disease.

04
How Do Rare Metabolic and Mitochondrial Disorders Affect the Visual System, and Can Functional Readouts Detect Metabolic Dysfunction Before Structural Loss Becomes Irreversible?
Audience A - Vision-focused
Audience B - CNS/Systemic

Quick Answer

Rare inherited metabolic disorders – including mitochondrial complex I deficiency, RPE-specific MCT2 insufficiency, and thyroid hormone transporter deficiency (AHDS) – produce retinal and optic nerve dysfunction that is detectable by OptoDrum before, or in parallel with, structural degeneration. Because the metabolic insult is defined and the functional timeline is trackable, these models are particularly suited to testing metabolic rescue strategies and to validating functional endpoints in IND-enabling preclinical studies.

The challenge

Metabolic rare diseases present a distinct challenge for preclinical researchers: the functional consequences of the metabolic defect often develop gradually and may precede visible structural pathology by weeks or months. Terminal endpoints – histology, electroretinography, electron microscopy – provide high-resolution snapshots but cannot resolve the functional trajectory within individuals. Moreover, in disorders such as AHDS where severe motor impairment is the dominant phenotype, conventional locomotor behavioural assays are so heavily confounded by the motor deficit that they cannot reliably report on CNS function.

The retina and optic nerve are among the most metabolically demanding tissues in the CNS, with photoreceptors and retinal ganglion cells particularly sensitive to mitochondrial energy failure, monocarboxylate transporter (MCT) dysfunction, and thyroid hormone-dependent myelination. This metabolic sensitivity makes the visual circuit an early warning system for systemic rare metabolic disease: functional visual changes detected by the optomotor reflex often precede, or parallel, CNS pathology that would otherwise require invasive sampling to detect. In models with severe motor phenotypes, the non-volitional, reflex-based nature of the OMR is a specific methodological advantage because it does not require voluntary locomotion.

For the toxicological dimension of mitochondrial dysfunction (rotenone, MPTP), see Ocular and CNS Toxicity Models. For therapeutic approaches targeting metabolic rescue, see Maintaining and Restoring Vision.

How Striatech products help

OptoDrum

Measures spatial visual acuity and contrast sensitivity via the subcortical optomotor reflex. In metabolic rare disease models, this provides a non-invasive readout of metabolic integrity in retinal circuits – detectable progressively from early metabolic compromise through structural degeneration – without requiring terminal tissue collection at each time point.

ScotopicKit

Measures rod-pathway (scotopic) visual acuity, which is particularly sensitive to mitochondrial and metabolic insults given the high energy demand of phototransduction in rod outer segments.

Non-aversive Animal Platform

Critical for metabolic rare disease models exhibiting muscle weakness, motor impairment, or debilitation; the restraint-free platform enables testing of animals that cannot tolerate conventional restraint procedures.

AcuiSee

Cortical operant acuity assessment; relevant for rare metabolic disorders where both subcortical (OMR) and cortical (perceptual) visual processing may be independently compromised, enabling dissection of the visual pathway level most affected.

Evidence from the Literature

  • Kinuthia et al (2025) JCI Insight.
  • Avrutsky et al (2022) Transl. Vis. Sci. Technol.

    Avrutsky et al – Characterised progressive retinal degeneration and functional decline in a mitochondrial complex I-deficient mouse model using a non-invasive ophthalmological test battery that included OptoDrum-based visual acuity measurement. Complex I-deficient mice developed progressive retinal degeneration detectable by the OMR, validating non-invasive visual function as a monitoring platform for retinal consequences of mitochondrial metabolic disease. Because complex I inhibition is also the mechanism of rotenone and MPTP neurotoxins, findings bridge the genetic rare-disease and toxicological paradigms. OptoDrum confirmed as primary endpoint.

  • Maity-Kumar et al (2022) Mol. Metab.

    Maity-Kumar et al – Validated the Mct8/Oatp1c1 double-knockout mouse as a preclinical model for Allan-Herndon-Dudley syndrome, a rare X-linked thyroid hormone transporter deficiency causing CNS hypomyelination and profound psychomotor impairment. OptoDrum measured visual function as a CNS functional readout in a model where severe motor impairment precludes reliable interpretation of locomotor-based assays. The non-volitional reflex-based nature of the OMR is a methodological advantage specific to this model class. Striatech instrument confirmed.

  • Chandler et al (2025) Proc Natl Acad Sci U S A.
    Journal Club →
    Feature →

    Chandler et al – Evaluated AAV-mediated RPE-specific overexpression of monocarboxylate transporter 2 (MCT2) as a metabolic rescue strategy for photoreceptor support. OptoDrum confirmed that MCT2 gene therapy preserved visual acuity above untreated degeneration controls, demonstrating that metabolic rescue of the RPE-photoreceptor lactate shuttle translates to a behaviourally measurable functional benefit. This study exemplifies how metabolic gene therapy targeting a transporter deficiency – applicable in principle to any rare disorder involving MCT dysfunction – can be validated using functional visual endpoints. OptoDrum confirmed.

05
How Are Innate-Immune Autoinflammatory Rare Syndromes and Translational Gene Therapy Programmes Validated Using Functional Visual Endpoints?
Audience A - Vision-focused

Quick Answer

Rare autoinflammatory syndromes caused by gain-of-function innate immune mutations (such as ALPK1/ROSAH and related innate immune kinase variants) produce genetically tractable models in which OptoDrum-measured visual function confirms that precision immunotherapy protects the retinal and optic nerve circuits. The same functional endpoint validates translational gene therapy programmes, including clinical-grade AAV vector preparations evaluated in IND-enabling preclinical studies.

The challenge

Rare autoinflammatory syndromes occupy a distinct niche in rare-disease research: unlike classic rare inherited retinal dystrophies driven by photoreceptor or RPE structural gene mutations, autoinflammatory syndromes such as ROSAH (retinal dystrophy, optic nerve oedema, splenomegaly, anhidrosis, headache) arise from gain-of-function mutations in innate immune signalling genes (ALPK1, NLRP3, STING-pathway components). These conditions bridge the fields of rheumatology, immunology, and ophthalmology, and present challenges for functional endpoint selection: the visual pathology involves both photoreceptor dysfunction and optic nerve inflammation, and treatment efficacy must be demonstrated at the functional circuit level rather than purely by inflammatory marker reduction.

Separately, gene therapy for rare retinal and CNS disorders is now reaching clinical translation, with GMP-manufactured viral vectors entering Phase I/II trials. For IND-enabling preclinical studies, it is critical to demonstrate that the pharmaceutical-grade vector preparation used in the clinical trial produces a functional visual benefit comparable to research-grade preparations. This requires a precise, sensitive, and repeatable functional endpoint – one that can distinguish between treated and untreated animals, and between clinical-grade and research-grade vector quality, in small preclinical cohorts.

For therapeutic approaches using gene therapy, optogenetics, and cell replacement in vision restoration contexts, see Maintaining and Restoring Vision. For the ocular immune-mediated dimension of autoinflammatory syndromes, see Ocular Inflammation and Immune-Mediated Eye Disease. For RGC-level functional consequences of autoinflammatory damage, see Retinal Ganglion Cell Pathology: Death, Dysfunction, and Functional Readouts Across Preclinical Models.

How Striatech products help

OptoDrum

Measures spatial visual acuity and contrast sensitivity via the optomotor reflex, providing a functional circuit-level endpoint to confirm that precision immunotherapy (e.g. ALPK1 inhibition) or gene therapy preserves RGC-mediated visual pathway integrity. Applicable to both autoinflammatory and gene therapy efficacy assessment.

AcuiSee

Measures cortical operant visual acuity; relevant for rare autoinflammatory syndromes with optic nerve or visual cortex involvement where confirming cortical-level visual processing recovery is important for translational claims.

Non-aversive Animal Platform

Reduces handling stress in post-treatment efficacy testing; particularly important in gene therapy cohorts where repeated handling stress could compromise post-surgical or post-injection recovery.

Evidence from the Literature

  • Kinuthia et al (2025) JCI Insight.
  • Fan et al (2025) Nat Commun.

    Fan et al – Reported the discovery of a selective ALPK1 inhibitor and demonstrated its efficacy in a ROSAH syndrome model, using OptoDrum to confirm that ALPK1 inhibition preserves RGC-dependent visual circuit function against innate immune-driven retinal and optic nerve inflammation. ROSAH syndrome, caused by gain-of-function ALPK1 mutations, represents a paradigmatic rare autoinflammatory ocular disease in which a single well-defined innate immune target is responsible for the full inflammatory phenotype, providing exceptional mechanistic tractability for precision immunotherapy development. OptoDrum confirmed.

  • Kozycki et al (2022) Ann. Rheum. Dis.

    Kozycki et al – Characterised a rare systemic autoinflammatory syndrome caused by gain-of-function innate immune signalling mutations and used OptoDrum to confirm that mutation-driven inflammation produces measurable functional visual circuit deficits including retinal dystrophy and neuroinflammatory visual pathway damage. Published in a rheumatology journal, this study exemplifies the cross-disciplinary nature of rare autoinflammatory ocular disease and demonstrates that visual function testing provides an endpoint accessible to researchers approaching these conditions from a systemic-immunology rather than ophthalmology perspective. OptoDrum confirmed.

  • Presa et al (2025) Commun Med (Lond).
    Journal Club →

    Presa et al – Evaluated a clinical-grade GMP AAV vector preparation in a rodent retinal degeneration model using OptoDrum as the primary in vivo functional endpoint. The study demonstrated that the clinical-grade preparation preserves visual acuity comparably to research-grade material, validating the manufacturing process for IND-enabling regulatory use. This is the only publication in the rare-disease cluster evidence base to explicitly use a clinical-grade rather than research-grade vector, making it specifically relevant to researchers preparing pre-IND or IND packages for rare retinal disease gene therapy programmes. OptoDrum confirmed.

Product Fit

Summary: Striatech Products supporting your research questions

Research Question OptoDrum ScotopicKit AcuiSee Photorefractor Keratometer DarkAdapt Non-aversive platform
Single-gene model tractability Yes   Yes       Yes
Longitudinal natural-history / therapeutic window Yes Yes       Yes Yes
Neuroinflammation amplifier in rare CNS disorders Yes           Yes
Metabolic / mitochondrial rare disorders Yes Yes Yes     Yes Yes
Autoinflammatory syndromes / gene therapy validation Yes   Yes       Yes
Measurement Modalities

Measuring Functional Visual Outcomes in Rare Disease: How Do Available Methods Compare?

Modality Invasiveness Repeatability within animal Suitable for severe motor impairment Automation 3Rs impact
OptoDrum (OMR, photopic and scotopic) None High (weekly or more frequent) Yes (reflex-based, no volitional locomotion required) Fully automated Reduces terminal sampling; enables within-animal designs
AcuiSee (cortical operant acuity) None High (after training) Moderate (requires minimal operant engagement) Automated reward delivery No terminal requirement; enrichment via task engagement
ERG (electroretinography) Moderate (anaesthesia, electrode contact) Moderate (anaesthesia stress) Low (anaesthesia risk in debilitated animals) Semi-automated Reduced by repeated anaesthesia stress
VEP (visual evoked potential) Moderate-high (electrode implant or scalp recording under anaesthesia) Low-moderate Low Low Implantation adds terminal or surgical cost
Histology / immunohistochemistry Terminal None (single time point per animal) Not applicable Semi-automated imaging Requires terminal sacrifice; high animal cost for longitudinal studies
OCT (optical coherence tomography) Low (topical anaesthesia or brief restraint) High Moderate (requires eye alignment) Semi-automated Structural only; complements functional OMR data
Supported by Striatech Products

Publications on Rare Disease

Great Research, Interactive

Journal Clubs related to Rare Disease

Featured image for “Journal Club: Gene-Agnostic Gene Therapy to Preserve Vision”
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Thursday, 11 Dec 2025

Journal Club: Gene-Agnostic Gene Therapy to Preserve Vision

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Constance Cepko, Ph.D. - Harvard Medical School: Genetics & Ophthalmology (Blavatnik Institute) • HHMI
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This Journal Club features innovative research by Harvard’s Cepko lab, exploring gene-independent strategies to preserve vision in retinitis pigmentosa and other genetic forms of blindness. Using AAVs to enhance metabolic support, including MCT2 expression in retinal pigment epithelial cells, they preserved cone photoreceptors and maintained color and daylight vision across diverse genotypes.
Featured image for “Journal Club: Postsynaptic Neuronal Activity Promotes Retinal Axon Regeneration”
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Wednesday, 21 Jun 2023

Journal Club: Postsynaptic Neuronal Activity Promotes Retinal Axon Regeneration

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Supraja Varadarajan, Ph.D. - Stanford University, School of Medicine, Huberman Lab
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This Journal Club provides insights into mechanisms that promote retinal ganglion cell (RGC) axon regeneration in vertebrates after optic nerve injury.
Featured image for “Journal Club: Inherited Retinal Dystrophy: Chronic Proinflammatory Signaling Accelerates the Rate of Degeneration”
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Wednesday, 05 Apr 2023

Journal Club: Inherited Retinal Dystrophy: Chronic Proinflammatory Signaling Accelerates the Rate of Degeneration

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T.J. Hollingsworth, PhD - University of Tennessee Health Science Center
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T.J. Hollingsworth presents his work where he characterized a new polygenic mouse model of inherited retinal dystrophies, the BXD32 mouse strain. He presents evidence that a proinflammatory environment in the retina supports and accelerates the degeneration of the retina and the loss of visual function.
Featured image for “Journal Club: Developing Retinal Gene Therapy for Zellweger Spectrum Disorder (ZSD)”
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Wednesday, 25 Jan 2023

Journal Club: Developing Retinal Gene Therapy for Zellweger Spectrum Disorder (ZSD)

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Catherine Argyriou, PhD - McGill University, Dept of Human Genetics
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Peroxisomal disorders and the PEX1-G844D mouse model for mild Zellweger Spectrum Disorder (ZSD), leads to retinal degeneration and vision loss. Catherine Argyriou will describe how her team used AAV8-mediated gene delivery to robustly and durably improve functional vision, retinal response, retinal structure, and biochemical metabolites in ZSD-mice.
Featured image for “Journal Club: In Vivo Modeling of Immune-mediated Optic Neuropathies”
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Wednesday, 09 Nov 2022

Journal Club: In Vivo Modeling of Immune-mediated Optic Neuropathies

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Oliver W. Gramlich, Ph.D. - The University of Iowa
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This presentation will outline the pathobiology and visual phenotype of immune mediated optic neuropathies that include Multiple Sclerosis (MS), Neuromylitis optica spectrum disorders (NMOSD), and Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD).
Featured image for “Journal Club: Anti-FcRn Treatment in Antibody-Associated Experimental Autoimmune Encephalomyelitis”
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Tuesday, 22 Mar 2022

Journal Club: Anti-FcRn Treatment in Antibody-Associated Experimental Autoimmune Encephalomyelitis

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Jana Remlinger, MSc - Department of Neurology, Inselspital, Bern University Hospital and Department for BioMedical Research (DBMR)
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Jana Remlinger et al. showed preserved visual function and ameliorated course of disease after anti-FcRn treatment in an experimental model using a monoclonal MOG-IgG to mimic MOGAD.
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Wednesday, 17 Nov 2021

Webinar: AcuiSee – Rodent Visual Acuity Using Behavioral Conditioning

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Dr. Jeffrey A Jamison - Experimentica Ltd.
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In this Webinar, Dr. Jeff Jamison will talk about “AcuiSee”, with which one can measure rodent vision based on an operant conditioning paradigm. Jeff is the developer of AcuiSee, and he now works as Director of In-Vivo Pharmacology at Experimentica.
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Thursday, 08 Oct 2020

Webinar: Visual Acuity as a Relevant Phenotype in Mouse Models of Rare Disease

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Zoë Bichler, PhD - The Jackson Laboratory
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Maximiliano Presa, PhD - The Jackson Laboratory
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The Jackson Laboratory will introduce their Neurobehavior Phenotyping Core, in which they also do visual acuity measurements. They will present two examples where the OptoDrum has been used to characterizte vision in animal models for rare disease: The Charcot-Marie-Tooth-disease, and Multiple-Sulfatase-Deficiency.
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Thursday, 02 Apr 2020

Journal Club: Measuring Visual Acuity and Contrast Sensitivity by Optomotor Reflex in Rodents

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Dr. Thomas Münch - Striatech
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Dr. Kaushikaram Subramanian - Max Planck Institute of Molecular Cell Biology and Genetics
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Prof. Volker Enzmann - Department of Ophthalmology, University of Bern
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In vision research, observing the optomotor reflex (OMR) is an important and widely established method for assessing visual acuity and contrast sensitivity in rodents. In this event, we will hear about several applications of OMR measuremnts, ranging from quantification of retinal degeneration to characterization of night vision.
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Related application areas, neighbouring research chapters, and the questions researchers ask most.

Application Area

Rare Disease

Individually uncommon, collectively affecting 300 million people — and uniquely tractable in preclinical research because the causal molecular lesion is known. The visual system is often a primary target or an early indicator of CNS pathology.

8
Research Chapters
5
FAQs answered
Main Field where Rare Disease is studied
Rare and Inherited CNS and Eye Disorders
Other relevant fields
Glaucoma and Optic Nerve Neurodegeneration
Maintaining and Restoring Vision
Neurodevelopment and Circuit Mechanisms
Neuroinflammation and Autoimmune CNS Disease
Ocular and CNS Toxicity Models
Ocular Inflammation and Immune-Mediated Eye Disease
Retinal Degeneration and Inherited Retinal Disease