Research Applications for Striatech Products

Glaucoma and Optic Nerve Neurodegeneration

The leading cause of irreversible blindness, driven by progressive retinal ganglion cell loss. Models span IOP-dependent and pressure-independent mechanisms, microglial and complement activation, and the search for neuroprotective therapies beyond pressure-lowering.
Introduction

What is Glaucoma and Optic Nerve Neurodegeneration?

Glaucoma is the leading cause of irreversible blindness worldwide, affecting an estimated 76 million people today and projected to exceed 110 million by 2040 as populations age (Tham et al., 2014, Ophthalmology). Pathologically, all major forms of glaucoma converge on a single final common pathway: the progressive degeneration of retinal ganglion cells (RGCs) and their axons within the optic nerve, culminating in permanent visual field loss. Elevated intraocular pressure (IOP) is the principal modifiable risk factor and the target of all currently licensed therapies; however, substantial RGC death and functional visual decline can occur at statistically normal IOP levels, indicating that pressure-independent mechanisms play a co-equal role once neurodegeneration is initiated. At the cellular and molecular level, glaucomatous neurodegeneration is driven by the convergence of multiple overlapping pathways. Microglial and astrocyte hyperactivation sustain a chronic neuroinflammatory environment in which TNF-α, complement cascade activation (particularly C1q, C3, and C3aR signalling), and reactive oxygen species collectively promote both apoptosis of the RGC soma and a Wallerian-like axon self-destruction programme regulated centrally by the NADase enzyme SARM1. The lamina cribrosa – where unmyelinated RGC axons traverse from the intraocular to the myelinated CNS environment – represents the primary mechanical and metabolic chokepoint, at which obstruction of axoplasmic transport initiates retrograde deprivation of neurotrophic support and triggers the degeneration cascade. Disease entities spanning primary open-angle glaucoma, normal-tension glaucoma, angle-closure glaucoma, exfoliation glaucoma, and rare inherited forms (such as myocilin-associated and optineurin-associated glaucoma) share this final degenerative pathway, even when their initiating insults differ substantially. Preclinical glaucoma research encompasses mechanistic characterisation of RGC death and inflammatory pathways, identification of neuroprotective and axon-regenerative targets, pharmacological and gene-based intervention testing, and evaluation of drug delivery systems. Across all these goals, objective and longitudinal measurement of visual function in living animals is essential to bridge molecular and structural findings to the functional endpoints that determine clinical relevance. Striatech's OptoDrum provides this measurement through a fully automated optomotor reflex (OMR) assay, enabling researchers to track spatial visual acuity and contrast sensitivity as continuous, quantitative readouts throughout disease progression and therapeutic intervention – without animal training, anaesthesia, or surgical access to the eye. 

Vision: A Window into the brain 

Why Are Visual Endpoints Relevant in Glaucoma and Optic Nerve Neurodegeneration Research?

For researchers whose primary interest is not clinical ophthalmology – including investigators studying CNS axon degeneration, axon regeneration, or neuroinflammation who use the optic nerve crush (ONC) model as a tractable in vivo platform – adding automated visual function measurement to an experimental workflow provides an orthogonal, functional endpoint that anatomical or histological readouts cannot supply on their own. Anatomical evidence of axon regrowth distal to a crush site, or rescue of RGC soma counts, is necessary but not sufficient evidence of functional reconnection: a treatment that preserves RGC numbers or promotes axon extension into the superior colliculus, but fails to restore the optomotor reflex, has not achieved functional visual recovery. The OptoDrum determines this non-invasively, at any time point, without interfering with the biology under study or the integrity of subsequent terminal analyses. Because the OMR is mediated by a subcortical reflex arc (retina → accessory optic system → nucleus of the optic tract → motor output), it reports directly on the integrity of the retino-recipient circuit rather than on cortical processing; for studies of axon regeneration and neuroprotection, this is precisely the circuit whose function needs to be demonstrated. For a focused treatment of RGC death as a distinct mechanistic topic, see the Retinal Ganglion Cell Death application page. For therapeutic restoration approaches building on the neuroprotection evidence described on this page, see also Maintaining and Restoring Vision.
Animal Models

What Are Common Animal Models For Glaucoma and Optic Nerve Neurodegeneration?

  • DBA/2J mice – A hereditary glaucoma model carrying mutations in Gpnmb and Tyrp1 that produce progressive iris disease and IOP elevation from approximately 6 months of age, followed by optic nerve degeneration and RGC loss. Visual acuity measured by OptoDrum declines in parallel with RGC loss, making this model well-suited to longitudinal natural-history studies and long-duration intervention trials in age-related glaucoma.
  • Microbead occlusion model (mice and rats) – Intracameral injection of polystyrene or magnetic microbeads obstructs aqueous outflow through the trabecular meshwork, producing controllable IOP elevation followed by RGC degeneration. The magnitude and duration of IOP elevation, and the resulting functional visual decline, can be titrated by adjusting bead concentration and schedule, making the model adaptable to both acute and chronic experimental designs.
  • Laser-induced IOP elevation – Photocoagulation of the trabecular meshwork or episcleral veins creates outflow obstruction with reliable RGC loss and measurable OptoDrum acuity decline. Unilateral designs use the contralateral eye as an internal control, and the degree of IOP elevation and RGC loss can be modulated by adjusting laser parameters.
  • Episcleral vein cauterisation (Morrison model, rats) – Cauterisation of episcleral veins elevates IOP chronically in rats, producing a well-characterised model of moderate progressive glaucoma with gradual RGC degeneration and visual decline that parallels the clinical course of chronic open-angle glaucoma.
  • Soluble guanylate cyclase (sGC) deficiency mice – Genetic disruption of the principal NO-cGMP signalling axis in trabecular meshwork cells recapitulates glaucoma-like RGC degeneration and functional visual decline; Bossardet et al. (2026) used OptoDrum to document this longitudinally across age, establishing sGC as a mechanistic driver of glaucomatous pathology.
  • Optic nerve crush (ONC) – A standardised surgical model in which the optic nerve is compressed briefly with calibrated forceps. ONC produces acute, near-complete RGC axon injury and rapid functional visual acuity loss detectable by OptoDrum within days to weeks. Because ONC does not involve IOP elevation, it is widely used as a pure axon injury model for studying neuroprotection, Wallerian degeneration, and axon regeneration – and serves as the primary in vivo platform for CNS axon biology groups for whom the optic nerve is a tractable CNS injury system.
  • Retinal ischemia-reperfusion injury (IRI) – Transient acute IOP elevation via anterior chamber cannulation (typically 30 to 90 minutes), followed by reperfusion, creates oxidative stress, complement activation, and RGC death mimicking the ischemic component of acute angle-closure glaucoma attacks. OptoDrum detects functional visual decline within one to two weeks of injury; this model has been used to evaluate complement-pathway inhibitors (Zhao et al., 2025, IOVS) and necroptosis inhibitors (Kim et al., 2024).
  • NMDA-induced excitotoxicity – Intravitreal injection of N-methyl-D-aspartate selectively kills RGCs through glutamate-receptor-mediated excitotoxicity without affecting photoreceptors, enabling isolated study of RGC-specific cell death programmes and neuroprotectants targeting excitotoxic pathways.
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 Can I Measure Visual Acuity and Contrast Sensitivity Reliably in Preclinical Glaucoma Models?
Audience A - Vision-focused

Quick Answer

Striatech’s OptoDrum measures spatial visual acuity (cycles per degree) and contrast sensitivity in awake, freely moving mice and rats via the automated optomotor reflex, without requiring animal training or anaesthesia. The assay takes approximately four minutes per animal and can be performed repeatedly without affecting the animal’s biology, making it ideal for longitudinal monitoring of glaucomatous visual decline. Both eyes can be assessed independently within a single session.

The challenge

Accurate, reproducible, and repeated measurement of visual function is the central methodological challenge in preclinical glaucoma research. The primary clinical endpoint of any therapeutic strategy – whether IOP-lowering, neuroprotective, or regenerative – is ultimately the preservation of visual function. Yet many preclinical studies rely exclusively on structural endpoints: RGC counts by immunohistochemistry, optic nerve axon density by electron microscopy, or retinal layer thickness by OCT. These endpoints are informative and necessary, but they are terminal or at minimum time-point-limited, they capture structure rather than function, and they cannot demonstrate that structural preservation translates into a functioning retino-cortical circuit. Electrophysiological endpoints such as ERG and VEP provide functional information but typically require anaesthesia (which affects retinal responses), specialised equipment and technical expertise, and are logistically demanding for high-throughput longitudinal applications.

The optomotor reflex offers a fundamentally different approach: it is a reflexive, subcortical behaviour that does not require the animal to have learned any task, that can be measured repeatedly in the same animal across weeks or months, and that directly reports on the integrity of the retino-brainstem pathway. Optomotor testing for visual acuity threshold determination was originally described by Prusky et al. (2004, Invest Ophthalmol Vis Sci) and further developed for bilateral measurement by Douglas et al. (2005, Vision Res). Striatech’s OptoDrum delivers this same validated paradigm in a fully automated, standardised format, eliminating experimenter-dependent stimulus control and inter-observer variability.

How Striatech products help

OptoDrum

Automatically measures photopic spatial visual acuity (cycles per degree) and contrast sensitivity threshold via the optomotor reflex in awake, freely moving mice and rats. Each eye is assessed independently; no training required; test duration approximately 4 minutes per animal. Enables daily or weekly longitudinal profiling across the full course of glaucomatous disease or experimental intervention.

AcuiSee

Measures visual acuity and contrast sensitivity via an operant, forced-choice paradigm requiring cortical visual processing and active decision-making. Complements OptoDrum for studies that also wish to assess suprathreshold visual perception or cognitive dimensions of visual function (for example, in aging or neurodegeneration co-morbidity contexts). Note that AcuiSee requires a training phase of 10 to 14 days.

Non-aversive Animal Platform

Allows animals to voluntarily enter the OptoDrum testing environment from their home cage via a tunnel-lid design. Reduces handling stress, which can introduce variability in the optomotor response; particularly relevant for aged DBA/2J mice or post-surgical animals who may be difficult to handle conventionally.

Evidence from the Literature

  • Kinuthia et al (2025) JCI Insight.
  • Mickevičius et al (2025) Exp Eye Res.

    In a comprehensive characterisation of a preclinical glaucoma model, the authors used OptoDrum to establish the time course over which structural RGC changes – cell death, axon damage, and optic nerve histopathology – map onto functional visual acuity decline. This study provides the benchmark correlation between structural glaucomatous endpoints and the OptoDrum readout, confirming that spatial acuity loss is a reliable functional correlate of progressive RGC neurodegeneration. OptoDrum was used directly in this study (confirmed by related-to-product-optodrum data-class tag).

  • Prusky, 2004

    The original description of the virtual optomotor system for rapid quantification of spatial visual acuity and contrast sensitivity in mice and rats without training. This study established the optomotor paradigm as a validated tool for tracking visual function longitudinally in disease models. Striatech’s OptoDrum implements this paradigm in a standardised, fully automated instrument.

  • Douglas, 2005

    This study described the methodology for bilateral, eye-specific measurement of visual acuity and contrast sensitivity using the optomotor reflex, demonstrating that each eye drives tracking in a specific direction and that the two eyes can therefore be assessed independently. This bilateral capability is implemented in OptoDrum and is directly relevant to unilateral glaucoma models where asymmetric disease is expected between treated and control eyes.

02
How Does Neuroinflammation Drive Retinal Ganglion Cell Loss in Glaucoma, and Can Targeting Inflammatory Pathways Preserve Visual Function?
Audience A - Vision-focused
Audience B - CNS/Systemic

Quick Answer

Neuroinflammation – mediated by TNF-α, complement cascade activation, and reactive microglial and glial responses – is a central driver of RGC death in both acute and chronic glaucoma. OptoDrum-confirmed studies show that targeting these inflammatory pathways pharmacologically, or suppressing glial activation, preserves measurable visual acuity in multiple preclinical glaucoma models, establishing the anti-inflammatory approach as a validated functional neuroprotective strategy.

The challenge

Neuroinflammation in glaucoma is not a secondary bystander response but an active amplifier of primary pressure-dependent and pressure-independent injury. Activated microglia produce TNF-α, which binds TNFR1 on RGCs and drives apoptosis via the extrinsic death pathway; simultaneously, complement proteins C1q, C3, and their receptor C3aR are upregulated at the optic nerve head and inner retina, promoting synaptic elimination, membrane-attack-complex formation, and phagocytic RGC clearance. Reactive astrogliosis further compromises the metabolic support provided to RGC axons at the lamina cribrosa. Each of these components represents a potential therapeutic target, but demonstrating that any intervention translates from a reduction in inflammatory markers or histological RGC rescue to a genuine improvement in functional vision has historically been difficult without a reliable, non-invasive functional readout. Research on neuroinflammation across multiple disease contexts is covered more broadly on the Neuroinflammation and Autoimmune CNS Disease application page. For information on how neuroinflammation also drives retinal degeneration beyond the RGC compartment, see the corresponding application page.

How Striatech products help

OptoDrum

Provides the functional confirmation endpoint for anti-neuroinflammatory interventions in glaucoma. Measures spatial acuity and contrast sensitivity longitudinally, enabling researchers to determine whether a reduction in TNF-α signalling, complement activation, or microglial hyperactivation achieved at the molecular level translates to preserved circuit-level visual performance.

AcuiSee

Provides a cortically mediated, operant visual acuity endpoint for neuroinflammation-driven RGC loss in glaucoma. Confirms whether anti-inflammatory interventions preserve learned visual discrimination and suprathreshold cortical visual processing, complementing the subcortical reflex readout from OptoDrum.

Evidence from the Literature

  • Kinuthia et al (2025) JCI Insight.
  • Li et al (2025) Neurosci Bull.

    This study demonstrated that TNF-α-mediated neuroinflammation drives optic nerve damage and RGC death in a glaucoma model, with OptoDrum confirming that TNF-α-induced structural loss translates to quantifiable functional visual acuity decline. The study provides direct evidence for the TNF-α axis as a driver of measurable visual impairment in glaucoma, not merely a marker of histological damage. OptoDrum used directly (confirmed by product data-class tag). Cross-relevance to the Neuroinflammation and Autoimmune CNS Disease application page.

  • Zhao et al (2025) Invest Ophthalmol Vis Sci.

    This study characterised complement C3/C3aR signalling as a neuroinflammatory cascade driving RGC dysfunction following retinal ischemia-reperfusion injury – a model relevant to acute IOP spike-induced RGC damage in angle-closure glaucoma. OptoDrum confirmed functional visual acuity loss resulting from complement-mediated injury. The study adds the complement pathway as a second mechanistic neuroinflammation target alongside TNF-α. OptoDrum used directly. Cross-relevance to the Neuroinflammation and Autoimmune CNS Disease and Trauma and Acute Injury pages. For a focused treatment of IRI models in glaucoma, see the Retinal Ischemia-Reperfusion Injury application page.

  • Zeng et al (2022) Biomolecules

    This study demonstrated that systemic treatment with pioglitazone, a PPAR-γ agonist, reduces neuroinflammation in a glaucoma model and – critically – preserves visual acuity as measured by OptoDrum, confirming that broad anti-inflammatory pharmacotherapy translates from reduced inflammatory histology to functional visual neuroprotection. This study establishes that the neuroinflammatory component of glaucomatous RGC loss is pharmacologically addressable with measurable functional benefit. OptoDrum used directly. Cross-relevance to Retinal Degeneration and Inherited Retinal Disease.

03
Do Neuroprotective Compounds and Gene Therapies Preserve or Restore Visual Function in Glaucoma Models?
Audience A - Vision-focused

Quick Answer

Multiple neuroprotective strategies – including SARM1-pathway targeting, RNA-based gene editing, nitric oxide-donating pharmacology, and novel drug delivery systems – have been shown to preserve OptoDrum-measured visual acuity in preclinical glaucoma models, demonstrating that structural RGC protection translates to measurable circuit-level functional benefit. OptoDrum provides the non-invasive functional endpoint that validates each intervention at the level that matters for clinical translation.

The challenge

IOP lowering alone does not halt glaucoma progression in a substantial proportion of patients, establishing a clear unmet need for IOP-independent neuroprotective strategies. Numerous candidate approaches have been advanced preclinically – targeting programmed cell death pathways, inflammatory mediators, metabolic support, and epigenetic dysregulation – but demonstrating that any of these translates from preserved RGC counts to genuinely preserved or restored visual function is the critical translational step. The structural rescue of RGCs that are subsequently non-functional, or the anatomical regrowth of axons that fail to establish synaptic contacts, does not constitute a meaningful preclinical outcome for therapeutic development. OptoDrum addresses this gap by providing a sensitive, non-invasive, and repeatable functional endpoint throughout an intervention study, enabling researchers to track the time course of protection, determine whether protection is sustained, and identify the optimal therapeutic window.

For a focused treatment of gene therapy approaches to vision rescue in retinal and optic nerve disease, see the Gene Therapy application page. For therapeutic approaches aimed at restoring vision after established damage, see also Maintaining and Restoring Vision.

How Striatech products help

OptoDrum

Provides the longitudinal functional endpoint for neuroprotective and gene therapy efficacy testing in glaucoma. Measures spatial acuity and contrast sensitivity non-invasively at any time point, enabling determination of the onset, magnitude, and durability of functional protection or restoration. Requires no animal training and can be performed on as many time points as the study demands without confounding subsequent terminal analyses.

AcuiSee

Provides a cortically mediated, operant visual acuity endpoint for neuroprotection and gene therapy studies in glaucoma. Confirms whether interventions that preserve RGCs and optic nerve integrity also maintain cortical visual discrimination – a higher-order functional confirmation the subcortical optomotor reflex does not capture.

Non-aversive Animal Platform

Reduces handling stress for post-surgical or debilitated animals, ensuring reliable optomotor responses from animals that may be compromised following intraocular injection or optic nerve surgery and that would otherwise produce unreliable data.

Evidence from the Literature

  • Kinuthia et al (2025) JCI Insight.
  • Zhao et al (2025) Adv Sci (Weinh).

    This study developed a high-fidelity RNA-targeting CRISPR-Cas system and demonstrated in a preclinical glaucoma model that gene-editing-mediated silencing of pathogenic targets preserves both RGC survival and OptoDrum-measured visual acuity. The neuroinflammation and glial- suppression co-tags indicate the Cas system also modulates the retinal inflammatory environment. This study represents the proof-of-concept application of precision RNA gene editing in glaucoma with direct functional validation. OptoDrum used directly. Cross-relevance to Retinal Degeneration and Inherited Retinal Disease.

  • Zeng et al (2024) Acta Neuropathol Commun.

    Genetic deletion of SARM1, the central NADase of the Wallerian axon self-destruction programme, reduced RGC death in a glaucoma model. Critically, OptoDrum confirmed that this structural axon and soma protection translated to preserved spatial visual acuity, establishing SARM1 as a therapeutic target whose functional benefit is demonstrable at the circuit level. SARM1 inhibition is an active area of neurodegeneration drug development. OptoDrum used directly. See also the Axon Degeneration application page for the broader axon degeneration context.

  • Pan et al (2025) J Med Chem.

    This medicinal chemistry study identified novel nitric oxide-donating compounds with dual mechanisms in glaucoma – IOP reduction and direct RGC neuroprotection. OptoDrum confirmed that these pharmacological effects preserved visual acuity, providing the translational functional validation required for the candidate compound programme. OptoDrum used directly.

  • Yang et al (2022) J. Med. Chem.

    An earlier study from the same NO-donor programme, providing historical depth for the pharmacological approach and confirming OptoDrum sensitivity to the functional effects of nitric oxide-based glaucoma pharmacology. OptoDrum used directly.

  • Lin et al (2022) Biomater. Sci.

    This biomaterials study showed that in situ-crosslinked hydrogel-mediated intraocular drug delivery preserved visual acuity in a glaucoma model as assessed by OptoDrum, illustrating that the functional readout is applicable not only to molecular target studies but also to delivery system validation. OptoDrum used directly.

04
How Do I Track Glaucoma Progression Longitudinally and Identify the Optimal Therapeutic Window?
Audience A - Vision-focused

Quick Answer

OptoDrum enables weekly or even daily longitudinal measurement of spatial visual acuity in awake animals throughout the full course of experimental glaucoma, from baseline through disease progression to endpoint. This non-invasive, repeated-measures approach allows precise identification of the onset of functional visual decline – and therefore of the therapeutic window – within individual animals, removing the need to sacrifice separate cohorts at multiple time points to reconstruct a progression curve.

The challenge

Identifying the optimal therapeutic window – the period during which RGCs are injured but not yet irreversibly lost, and therefore still rescuable – is one of the most practically important and methodologically demanding aspects of preclinical glaucoma research. Traditional approaches infer progression from structural data (RGC counts, nerve fibre layer thickness) collected in separate cohorts at pre-specified time points, which are expensive in animal numbers, confound between-subject variability with temporal progression, and fail to capture within-individual inflection points in functional decline. A functional biomarker that can be measured repeatedly in the same animal – as OptoDrum provides – transforms the experimental design: instead of inferring population-level curves from cross-sectional cohorts, the researcher can establish individual trajectories and identify the precise moment of functional onset for each animal, then stratify intervention timing accordingly. This precision is particularly important in aging-disease interactions (such as age-dependent glaucoma in DBA/2J mice) where the onset of IOP elevation and functional decline is variable between individuals. For researchers studying rare or inherited glaucoma subtypes, the model selection question – which genetic background provides the most relevant visual phenotype – is a prerequisite for longitudinal programme design, and OptoDrum provides the visual phenotyping needed to make that comparison.

For information on rare and inherited glaucoma models, see the Rare and Inherited CNS and Eye Disorders application page. For the relationship between myopia, axial elongation, and secondary glaucomatous optic nerve damage, see the Myopia, Refractive Development and Eye Growth and Myopia application pages. For end-stage outcomes including blindness, see the corresponding application page.

How Striatech products help

OptoDrum

Measures spatial acuity and contrast sensitivity longitudinally at any frequency (weekly, biweekly, or daily in acute models). Provides a within-subject functional timeline that enables precise identification of functional decline onset, plateau, and response to intervention. No animal training or anaesthesia; approximately 4 minutes per animal; compatible with concurrent structural assessments at the same time points.

AcuiSee

Provides a cortically mediated, operant visual acuity endpoint for longitudinal tracking of glaucoma progression. May reveal progressive impairment in learned visual discrimination as RGC loss advances, complementing the subcortical reflex trajectory from OptoDrum.

Non-aversive Animal Platform

Ensures consistent optomotor responses across repeated testing sessions for aged, handled-sensitive, or chronically diseased animals – reducing the test-to-test variability that can obscure the early stages of functional decline when the therapeutic window is most critical to identify.

Evidence from the Literature

  • Kinuthia et al (2025) JCI Insight.
  • Bossardet et al (2026) Sci Rep.

    This study tracked functional visual acuity longitudinally using OptoDrum in sGC-deficient mice across age, documenting the natural history of progressive glaucoma-like visual decline in a genetically defined model. By measuring the same animals at multiple time points, the study established the within-individual course of functional deterioration – precisely the information needed to identify the therapeutic window for interventions targeting the NO-sGC-cGMP axis in glaucoma. OptoDrum used directly.

  • Kuchtey et al (2024) Am J Ophthalmol.

    This systematic evaluation of mouse models for rare and inherited glaucoma used OptoDrum to phenotype the visual deficit severity across candidate genetic backgrounds, providing the functional characterisation needed to select the most appropriate model for a longitudinal therapeutic programme. Establishing the baseline phenotype and rate of decline is a prerequisite for designing an appropriately powered intervention study with defined therapeutic windows. OptoDrum used directly. Cross-relevance to Rare and Inherited CNS and Eye Disorders.

  • Insignares et al (2025) Int J Mol Sci.

    This study characterised progressive ocular axial elongation and secondary optic nerve damage, using OptoDrum to document the functional visual decline that accompanies structural RGC dysfunction. Although the primary finding concerns axial growth (cross-relevant to Myopia, Refractive Development and Eye Growth), the secondary optic nerve damage and functional decline are directly relevant to the longitudinal tracking design in high-myopia-associated glaucoma models. OptoDrum used directly.

05
How Does Aging Interact with Glaucomatous Neurodegeneration, and Can Visual Function Serve as a Readout of Age-Glaucoma Pathology?
Audience A - Vision-focused
Audience B - CNS/Systemic

Quick Answer

Aging amplifies virtually every component of glaucomatous neurodegeneration – increasing basal neuroinflammation, impairing RGC metabolic resilience, reducing the capacity for axon repair, and accelerating the epigenetic dysregulation associated with RGC loss. OptoDrum-confirmed studies demonstrate that age-associated visual decline is measurable and, in a landmark study, partially reversible through epigenetic reprogramming gene therapy.

The challenge

Age is the single largest non-modifiable risk factor for glaucoma: the prevalence of the disease rises steeply after 60 years of age, and normal aging itself reduces RGC density, degrades axon transport efficiency, and shifts the microglial phenotype toward a proinflammatory state that amplifies pressure-dependent injury. Preclinical researchers working with aging glaucoma models therefore face compounded variability: the degree of IOP elevation, the rate of RGC loss, and the time course of functional visual decline all vary between individual animals in an age-dependent way that is difficult to control by group assignment alone. A functional biomarker that tracks each animal individually – as the OptoDrum provides – is therefore particularly valuable in the aging-glaucoma intersection, where within-group variance is high and individual inflection points matter for therapeutic window determination. Beyond tracking decline, an important emerging question is whether age-related epigenetic changes that reduce RGC resilience can be pharmacologically reversed; the OSK gene therapy programme (Karg et al., 2023) has demonstrated proof-of-concept for this reversal, with OptoDrum as the primary endpoint for functional vision recovery. For information on aging as a systemic CNS process with broad implications for visual function, see the Systemic Aging and CNS Decline application page. For the cluster-specific treatment of aging as a visual and ocular process, see the Aging application page. For therapeutic approaches building on the neuroprotection literature described here, see also Maintaining and Restoring Vision.

How Striatech products help

OptoDrum

Tracks age-related visual acuity and contrast sensitivity decline longitudinally in the same animal across weeks and months. In aging models (such as DBA/2J mice or sGC-deficient aging cohorts), within-animal tracking allows precise determination of when age-related functional decline begins in each individual, avoiding the misclassification that arises from cross-sectional sampling of an inherently variable aging population.

AcuiSee

In aging studies where cortical processing and visual cognitive function are also of interest – for example, in studies examining both retinal and cortical aspects of age-related visual decline – AcuiSee’s operant paradigm complements the OptoDrum’s subcortical OMR endpoint by assessing the suprathreshold, decision-making dimension of visual perception.

Non-aversive Animal Platform

Particularly important for aged animals, which are more sensitive to handling stress and more likely to produce inconsistent optomotor responses under conventional restraint. The tunnel-lid design allows voluntary entry from the home cage, reducing the confounding effect of stress-induced behavioural suppression in aged cohorts.

Evidence from the Literature

  • Kinuthia et al (2025) JCI Insight.
  • Karg et al (2023) Cell Reprogram.

    This landmark study demonstrated sustained recovery of visual acuity in an aging glaucoma mouse model following AAV-mediated delivery of OSK (Oct4/Sox2/Klf4) epigenetic reprogramming factors. OptoDrum served as the primary functional endpoint, showing that acuity lost to combined aging and glaucomatous damage was measurably and durably restored following OSK treatment. This study represents the most direct available evidence that OptoDrum can detect functional vision recovery – not only decline – in an age-glaucoma model, and it provides the benchmark functional outcome for the epigenetic reprogramming approach. OptoDrum used directly. Cross-relevance to Systemic Aging and CNS Decline and to Maintaining and Restoring Vision.

  • Hollingsworth et al (2022) Front. Pharmacol.

    This study examined chronic proinflammatory conditions in an aging mouse model and documented progressive visual acuity decline using OptoDrum. While the primary focus is on aging-related retinal degeneration (cross-relevant to Retinal Degeneration and Inherited Retinal Disease and Systemic Aging and CNS Decline), the chronic neuroinflammation-aging interaction it characterises is mechanistically parallel to the inflammatory amplification of pressure-independent RGC loss in age-related glaucoma. OptoDrum used directly.

06
Can Optic Nerve Injury and Ischemia-Reperfusion Models Inform Neuroprotective and Regenerative Strategies Relevant to Glaucoma?
Audience A - Vision-focused
Audience B - CNS/Systemic

Quick Answer

Optic nerve crush (ONC), retinal ischemia-reperfusion injury, and acute IOP elevation models provide well-controlled, rapid-onset injury systems that are widely used to evaluate neuroprotective compounds, axon-regenerative strategies, and mechanistic targets relevant to glaucoma. OptoDrum-confirmed studies in these models have identified RIP1 kinase inhibition, zinc transporter deletion, erythropoietin administration, and dopaminergic circuit modulation as candidates with demonstrated functional visual benefit. Critically, OptoDrum provides the functional validation that confirms structural neuroprotection has translated to circuit-level visual preservation.

The challenge

ONC and IRI models occupy an important strategic position in preclinical glaucoma research: they produce rapid, reproducible, and quantifiable injury to the optic nerve and RGC population within a compressed time frame, enabling high-throughput evaluation of candidate neuroprotective and regenerative interventions before committing to the longer and more resource-intensive chronic glaucoma models. A central challenge in interpreting data from these acute models is demonstrating that the structural outcomes most commonly reported – RGC survival counts, axon density measurements, or anterograde axon tracer results – translate to genuine functional visual improvement. Anatomical evidence of axon regrowth following a regeneration-promoting intervention, for example, does not confirm that the regenerated axons have re-established functional synaptic contacts with their targets in the brain. OptoDrum addresses this directly: it measures the functional optomotor output of the retino-brainstem circuit and can distinguish animals with genuine visual circuit recovery from those with structural rescue that has not been functionally integrated. These acute injury models are also the primary platform for CNS axon biology groups not primarily working in ophthalmology; for these researchers, visual function measurement with OptoDrum adds a validated functional endpoint to what would otherwise be a purely anatomical or molecular experimental output.

For information on the broader Trauma and Acute Injury application context, see the Trauma and Acute Injury application page. For focused treatments of the specific cluster topics involved, see the Optic Nerve Damage, Axon Degeneration, Optic Nerve Regeneration, and Retinal Ischemia-Reperfusion Injury application pages. For inherited forms of optic neuropathy – such as Wolfram syndrome optic atrophy – in which metabolic failure and neuroinflammation drive progressive optic nerve degeneration through mechanisms overlapping with those described here, see the Rare and Inherited CNS and Eye Disorders application page. For optic neuritis as a distinct inflammatory optic neuropathy entity, see the Optic Neuritis application page.

How Striatech products help

OptoDrum

Measures functional visual acuity and contrast sensitivity at any time point following ONC, IRI, or acute IOP elevation, providing the critical functional endpoint that confirms whether structural neuroprotection or axon regeneration has translated to circuit-level visual recovery. Non-invasive, requires no training, takes approximately 4 minutes per animal; can be performed as frequently as needed without interfering with concurrent molecular or histological analyses.

AcuiSee

Provides a cortically mediated, operant visual acuity endpoint for optic nerve injury and ischaemia-reperfusion studies. Assesses whether neuroprotective or regenerative interventions restore learned visual discrimination, confirming cortical visual processing recovery beyond subcortical reflex improvement.

Non-aversive Animal Platform

Reduces handling stress for post-surgical animals recovering from ONC or IRI procedures, ensuring consistent optomotor responses in the early post-injury period when animals may be physically compromised and in which data quality is most critical for identifying the temporal profile of functional decline and recovery.

DarkAdapt

When scotopic (rod-mediated) visual function is also of interest – for example, in ONC studies examining whether rod pathways are differentially spared relative to cone pathways, or in inherited optic neuropathy models where rod function may decline earlier – DarkAdapt provides the light-tight housing needed to dark-adapt animals prior to scotopic OMR testing with the OptoDrum ScotopicKit extension.

Evidence from the Literature

  • Kinuthia et al (2025) JCI Insight.
  • Kim et al (2024) Cell Death Differ.

    RIP1 kinase inhibition protected RGCs from necroptotic death and attenuated neurovascular injury in a retinal ischemia-reperfusion model. OptoDrum confirmed that this structural neuroprotection translated to preserved visual acuity, establishing RIP1 kinase as a validated functional neuroprotective target in an acute glaucoma-relevant injury setting. OptoDrum used directly. Cross-relevance to Retinal Degeneration and Inherited Retinal Disease and Trauma and Acute Injury.

  • Liu et al (2023) Neural Regen Res.

    Selective deletion of a zinc transporter reduced axon degeneration and promoted optic nerve regeneration following ONC, with OptoDrum confirming that structural improvements in axon integrity corresponded to improved functional visual acuity. This study identifies zinc transporter modulation as a candidate neuroprotective-regenerative target with demonstrated functional benefit in the ONC model. OptoDrum used directly. See also the Axon Degeneration and Optic Nerve Regeneration application pages.

  • Eghbali et al (2023) Cell J.

    Erythropoietin protected RGCs from degeneration following optic nerve injury partly by suppressing reactive glial activation. OptoDrum confirmed that the structural neuroprotection and anti-neuroinflammatory effects of EPO translated to preserved visual acuity, supporting EPO’s translational potential for optic neuropathies with a glial-mediated inflammatory component. OptoDrum used directly. See also the Glial Suppression application page.

  • Li et al (2023) Life Sci. Alliance

    Vitamin C (ascorbic acid) provided antioxidant neuroprotection for RGCs in an optic nerve damage model, with OptoDrum confirming that antioxidant-mediated structural RGC protection translated to preserved visual acuity. The study illustrates OptoDrum’s sensitivity to clinically available, antioxidant neuroprotective interventions. OptoDrum used directly. Cross-relevance to Trauma and Acute Injury.

  • Rossi et al (2023) Elife

    MCT1-dependent metabolic failure in oligodendrocytes was shown to drive secondary neuroinflammation and progressive optic nerve degeneration in a Wolfram syndrome model, with OptoDrum measuring progressive visual acuity loss as the functional readout of optic neuropathy. This study is relevant to the broader optic nerve degeneration literature as a demonstration that metabolic support failure – rather than IOP or direct axonal injury – can drive a clinically significant optic neuropathy with measurable functional consequences. OptoDrum used directly. For the full inherited optic neuropathy context, see Rare and Inherited CNS and Eye Disorders.

Product Fit

Summary: Striatech Products supporting your research questions

Research Question OptoDrum ScotopicKit AcuiSee Photorefractor Keratometer DarkAdapt Non-aversive platform
Measuring visual acuity and contrast sensitivity Yes   Yes       Yes
Neuroinflammation and RGC loss Yes   Yes        
Neuroprotection and gene therapy Yes   Yes       Yes
Longitudinal tracking Yes   Yes       Yes
Aging and glaucoma Yes   Yes       Yes
ONC and acute injury models Yes Yes* Yes     Yes* Yes

* ScotopicKit and DarkAdapt are relevant for ONC and acute injury models when scotopic (rod-mediated) visual function is also a study endpoint. 

Measurement Modalities

Measuring Functional Visual Outcomes in Glaucoma and Optic Nerve Neurodegeneration: How Do Available Methods Compare?

Glaucoma preclinical research uses a range of modalities to assess the consequences of RGC degeneration and the efficacy of interventions. The table below compares the principal options across dimensions most relevant to research design decisions. Striatech's tools are most valuable when combined with structural and electrophysiological endpoints, not as replacements for them.
Modality What It Measures Invasiveness Repeatability in the same animal Training required Automation 3Rs relevance
OptoDrum (Striatech) Spatial visual acuity and contrast sensitivity via optomotor reflex (subcortical) Non-invasive; no anaesthesia High; can be performed daily None Fully automated Refinement (no restraint, no anaesthesia); enables Reduction (replaces some terminal cohorts)
AcuiSee (Striatech) Visual acuity and contrast sensitivity via operant forced-choice (cortical) Non-invasive; food restriction required High after training phase 10 to 14 days Automated after training Refinement; provides psychophysical cortical endpoint complementary to OMR
Scotopic ERG Rod and cone photoreceptor function; inner retinal function (b-wave, pSTR) Moderate; typically requires anaesthesia and pupil dilation Moderate; anaesthesia imposes practical limits on frequency Operator skill required Semi-automated Moderate; anaesthesia constitutes a physiological perturbation
Pattern ERG (PERG) RGC-specific electrophysiological response to patterned stimuli Moderate; requires anaesthesia and corneal electrode placement Moderate Operator skill required Semi-automated Moderate; more specific to RGC function than flash ERG; complements OMR
Visual Evoked Potential (VEP) Cortical response to visual stimulation; assesses the full retino-cortical pathway Invasive; requires surgical electrode implantation in most protocols Low to moderate depending on electrode implant High; surgical implantation and signal processing expertise Low Lower 3Rs score due to surgical invasiveness; cortical endpoint complements OMR
Optical coherence tomography (OCT) Retinal layer thicknesses including RNFL and GCL; structural endpoint only Low to moderate; typically requires anaesthesia or restraint for rodents High Operator skill required for image acquisition and segmentation Semi-automated segmentation Structural endpoint; does not measure functional vision; complements OMR
Histological RGC counting RGC soma and axon density at a single time point; structural endpoint only Terminal None (terminal) Moderate histological expertise Partially automated (image analysis) Terminal; limits the number of time points per animal; replaced by repeated OMR for longitudinal studies
Supported by Striatech Products

Publications on Glaucoma and Optic Nerve Neurodegeneration

Great Research, Interactive

Journal Clubs related to Glaucoma and Optic Nerve Neurodegeneration

Featured image for “Journal Club: RIP1 Inhibition Protects Retinal Ganglion Cells in Preclinical Glaucoma Models”
Q&A available
Watch now
Wednesday, 18 Jun 2025

Journal Club: RIP1 Inhibition Protects Retinal Ganglion Cells in Preclinical Glaucoma Models

Image
Bo Kyoung Kim, Ph.D. - Roche Pharma Research & Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd.
Image
This Journal Club features innovative research by Kim et al., who revealed that inhibiting RIP1 kinase protects retinal ganglion cells in preclinical glaucoma models. Their work demonstrates that targeting necroptosis and inflammation can prevent cell loss and functional decline, directly linking genetic risk to inflammatory degeneration and highlighting RIP1 as a promising therapeutic target for neuroprotection in glaucoma.
Featured image for “Journal Club: Aging and Injured Retinal Ganglion Cells Can Be Rejuvenated by Epigenetic Reprogramming”
Watch now
Thursday, 27 Feb 2025

Journal Club: Aging and Injured Retinal Ganglion Cells Can Be Rejuvenated by Epigenetic Reprogramming

Image
Bruce R. Ksander, Ph.D. - Schepens Eye Institute of Mass Eye & Ear, Harvard Medical School, Department of Ophthalmology
Image
This Journal Club highlights groundbreaking work by Harvard Medical School scientist Bruce R. Ksander and his team. They were able to reverse aging in retinal ganglion cells, improving visual function after injury or in disease.
Featured image for “Webinar: AcuiSee – Rodent Visual Acuity Using Behavioral Conditioning”
Watch now
Wednesday, 17 Nov 2021

Webinar: AcuiSee – Rodent Visual Acuity Using Behavioral Conditioning

Image
Dr. Jeffrey A Jamison - Experimentica Ltd.
Image
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.
Featured image for “Journal Club: The role of Nogo-A in visual deficits induced by retinal injury.”
Q&A available
Watch now
Thursday, 28 Jan 2021

Journal Club: The role of Nogo-A in visual deficits induced by retinal injury.

Image
Julius Baya Mdzomba, PhD - Université Laval
Image
Nogo-A, an inhibitor of neural growth, prevents regeneration after injury. Blocking of Nogo-A aides recovery, also in the visual system after retinal damage. Baya Mdzomba show with our OptoDrum that visual behavior benefits from Nogo-A neutralization after retinal damage typically found in diabetic retinopathy or glaucoma.
Keep exploring

Related application areas, neighbouring research chapters, and the questions researchers ask most.

Research Chapter

Glaucoma and Optic Nerve Neurodegeneration

The leading cause of irreversible blindness, driven by progressive retinal ganglion cell loss. Models span IOP-dependent and pressure-independent mechanisms, microglial and complement activation, and the search for neuroprotective therapies beyond pressure-lowering.

16
Application Areas
6
FAQs answered
Part of Eye & Retinal Disease

Main Application Areas

Glaucoma
Optic Nerve Damage
Retinal Ganglion Cell Pathology

Additional Topics

Aging
Axon Degeneration
Blindness
Gene Therapy
Glial Suppression
Myopia
Neuroinflammation
Neurovascular Injury
Optic Nerve Regeneration
Optic Neuritis
Rare Disease
Retinal Degeneration
Retinal Ischemia-Reperfusion Injury