Ocular and CNS Toxicity Models

Measures spatial visual acuity (cycles per degree) and contrast sensitivity via the optomotor reflex in awake, freely moving rodents. In NaIO3 and other chemical retinal toxin models, tracks the progressive functional consequence of RPE and photoreceptor degeneration non-invasively and longitudinally. Fully automated; no anaesthesia or training required; less than 10 minutes per animal.

Provides a cortically mediated, operant visual acuity endpoint for chemical toxin-induced retinal degeneration models. Assesses whether toxin damage impairs learned visual discrimination and suprathreshold visual perception, complementing the subcortical reflex readout from OptoDrum.

ScotopicKit

Extends OptoDrum testing to scotopic (rod-mediated) conditions in steps of 1 log unit luminance. In sodium iodate models, where rod photoreceptors are among the first cells affected by secondary RPE loss, scotopic visual acuity testing can detect rod-specific functional deficits before photopic acuity decline becomes apparent, providing an earlier-window functional readout.

DarkAdapt

Light-tight, ventilated housing for dark-adapting animals prior to scotopic OMR testing. Ensures reproducible and consistent dark-adaptation across all time points in longitudinal studies, a prerequisite for reliable scotopic acuity measurements.

Evidence from the Literature

Kinuthia et al (2025) JCI Insight.
Carido et al (2014) IOVS
This foundational study characterised the time course of RPE ablation, photoreceptor degeneration, and visual function decline following systemic NaIO3 injection in mice, using OptoDrum to measure visual acuity as the primary in vivo functional endpoint. It established that the NaIO3 model produces a reproducible and quantifiable optomotor acuity deficit that parallels histological degeneration, validating OptoDrum as the appropriate functional readout for this chemical toxin model. The study also carries age-related-macular-degeneration and systemic-aging-and-cns-decline tags, reflecting the AMD relevance of the model.
Moriguchi et al, 2018
Moriguchi and colleagues provided an electrophysiological characterisation of the NaIO3 model in rats using ERG, documenting the temporal relationship between RPE ablation and photoreceptor functional decline. This study used a custom electroretinographic approach; Striatech’s OptoDrum delivers a complementary behavioural endpoint in the same model, providing the OMR-based acuity readout that ERG alone cannot supply.
Bhutto and colleagues, 2012
This review provides the scientific context for why RPE ablation models such as the NaIO3 paradigm are considered translational for AMD. The biological rationale for using OptoDrum-measured visual acuity as a functional AMD endpoint rests on the RPE–photoreceptor–visual pathway architecture described in this work.

Can Photorefraction Detect Toxicant-Induced Changes in Ciliary Function and Refractive State?

Audience A - Vision-focused

Audience B - CNS/Systemic

Quick Answer

Yes. The Photorefractor measures the refractive state of the rodent eye in diopters using eccentric infrared photorefraction, and two published studies using Striatech’s Photorefractor have demonstrated that both pilocarpine-mediated calcium cytotoxicity and senescence-associated oxidative stress in ciliary muscle cells produce measurable changes in refractive state detectable in vivo. This makes Photorefraction a viable, non-invasive functional readout for pharmacological toxicity and cytoprotection studies targeting the anterior segment and ciliary apparatus.

The challenge

The ciliary muscle and lens are the anatomical structures governing accommodation – the dynamic adjustment of refractive power that allows the eye to focus at different distances. Toxicants that cause calcium overload, oxidative stress, or cellular senescence in these structures disrupt both cellular integrity and mechanical function, with direct consequences for the refractive state of the eye. Yet the functional consequence of ciliary toxicity at the whole-eye level has historically been difficult to measure non-invasively in small laboratory rodents: slit-lamp biomicroscopy requires restraint and anaesthesia, and measuring accommodative amplitude in a mouse or rat is technically demanding.

Eccentric infrared photorefraction resolves this problem. The Photorefractor analyses the pattern of infrared light reflected from the retina through the pupil, computing the refractive state (spherical equivalent) of the eye automatically from the asymmetry of the reflective profile. Because the calculation integrates the optical contributions of the cornea, lens, and vitreous, it is sensitive to any structural or functional change in these components that shifts the refractive balance of the eye. When pilocarpine, for example, drives excessive calcium accumulation in ciliary cells and thereby disrupts ciliary muscle contractility, the Photorefractor detects the resulting shift in resting refractive state (Gao et al, 2024, FASEB J). Similarly, when age-related or oxidant-induced senescence impairs ciliary muscle function, the consequent myopic shift or accommodation loss is quantified in diopters by the same instrument (Gao et al, 2024, Phytomedicine).

This approach is most directly relevant to researchers working on myopia pharmacology, lens biology, and anterior segment toxicology. For a broader treatment of refractive development and myopia models, see the Myopia, Refractive Development and Eye Growth application page. For the intersection of ciliary aging and systemic toxicological processes, see the Systemic Aging and CNS Decline application page. For a focused discussion of the toxicity cluster, see the Toxicity cluster page, and for the aging-specific angle, see the Aging cluster page.

How Striatech products help

Measures the refractive state (spherical equivalent in diopters) of the rodent eye by eccentric infrared photorefraction in alert, freely moving animals. Captures the optical consequence of ciliary muscle toxicity, lens toxicity, or anterior segment degeneration as a shift in resting refractive state. Automated measurement; no anaesthesia or restraint required; compatible with mice, rats, guinea pigs, and chickens.

Keratometer

Measures corneal radius of curvature via reflection of an infrared LED ring from the corneal surface. When toxicant-induced changes affect corneal geometry as well as internal optics, the Keratometer provides a complementary structural endpoint that isolates the corneal contribution to refractive change. Used in combination with Photorefractor for a complete anterior segment optical profile.

Evidence from the Literature

Kinuthia et al (2025) JCI Insight.
Gao et al (2024) FASEB J.
Gao and colleagues demonstrated that pilocarpine at elevated doses drives calcium-mediated cytotoxicity in ciliary and lens cells, with the Photorefractor documenting the refractive consequence of this toxicity in vivo. The study establishes dose-dependent relationships between pilocarpine toxicity and refractive shift, providing both a mechanistic characterisation of the toxicity and validation of Photorefraction as its functional readout. Striatech Photorefractor was used. This study also carries a myopia-refractive-development-and-eye-growth tag, reflecting its relevance to experimental myopia pharmacology.
Gao et al (2024) Phytomedicine
This study showed that lutein attenuates oxidative-stress-induced senescence in ciliary muscle cells and preserves refractive state as measured by Photorefractor. The work demonstrates that a cytoprotective antioxidant intervention against age-related ciliary toxicity produces a measurable optical benefit detectable in vivo, validating Photorefraction as a functional endpoint for evaluating anterior segment cytoprotective compounds. Striatech Photorefractor was used.
Schaeffel et al, 1988
This landmark study established the foundational principles of eccentric photorefraction as a method for measuring refractive state in small-eyed animals, providing the methodological underpinning for the Photorefractor instrument distributed by Striatech. The original apparatus was a custom laboratory system; Striatech’s Photorefractor delivers the same measurement principle in an automated, commercial format validated for mice, rats, guinea pigs, and chickens.

Do Fluorescent Reporter Genes or Viral Constructs Used in Preclinical Experiments Cause Retinal Toxicity That Could Confound My Results?

Audience A - Vision-focused

Quick Answer

Potentially, yes – and OptoDrum provides the functional screen to determine whether they do. Zhang et al (2024) demonstrated that tdTomato expression in retinal neurons causes dose-dependent retinal ganglion cell dysfunction detectable by the optomotor reflex, with functional deficits apparent before histological damage becomes statistically significant. Any researcher using fluorescent reporters or viral vectors in retinal or CNS models with visual endpoints should include an OptoDrum baseline assessment before and after construct introduction as a standard safety control.

The challenge

Fluorescent reporter genes – tdTomato, mCherry, GFP, YFP, and their variants – are ubiquitous tools in modern neuroscience and ophthalmology. They are used to label specific cell populations, report on promoter activity, track transplanted cells, and validate viral vector transduction efficiency. The implicit assumption in most experimental designs is that the reporter gene itself is biologically inert and does not affect the cells it labels. For studies using visual function as an endpoint, this assumption is critical: if the reporter gene is itself toxic to RGCs or other retinal neurons, it will produce a visual acuity deficit that is indistinguishable from the disease-related or treatment-related deficit the researcher is attempting to measure.

Zhang et al (2024) challenged this assumption directly, showing that tdTomato expression in retinal neurons produces progressive RGC dysfunction measurable by OptoDrum, with the degree of dysfunction correlating with expression level (Zhang et al, 2024, Exp Eye Res). This finding has broad implications for any laboratory using tdTomato as a reporter in retinal gene therapy studies, transgenic model characterisation, or cell-transplantation tracking experiments. It also illustrates the sensitivity of the OptoDrum as a toxicity screen: because the OMR is driven by the integrated output of the photoreceptor-to-RGC pathway, it detects subthreshold functional compromise before overt histological RGC loss becomes apparent, making it a more sensitive early-warning tool than terminal histology alone.

The same principle applies to viral vectors (AAV, lentivirus, adenovirus) used for gene therapy or optogenetic tool delivery in retinal research. The vector capsid, the transgene product, and the promoter-driven expression level can all potentially produce ocular toxicity at high titres. OptoDrum screening before and after intravitreal or subretinal injection provides a non-invasive safety check that can be incorporated into any vector characterisation protocol without additional animal use or surgical procedures. For the broader cluster of retinal ganglion cell dysfunction endpoints, see the Retinal Ganglion Cell Dysfunction cluster page. For the general toxicity cluster, see the Toxicity cluster page.

How Striatech products help

Provides a rapid, non-invasive functional screen for reporter gene or viral vector retinal toxicity. Measures visual acuity and contrast sensitivity before and after construct introduction in the same animal, detecting RGC pathway dysfunction with sensitivity to subthreshold functional changes that precede overt histological loss. No anaesthesia or additional surgical procedures required; approximately 4 minutes per animal.

Provides a cortically mediated, operant visual acuity endpoint for detecting reporter gene and viral construct retinal toxicity. Assesses whether construct-induced damage impairs learned visual discrimination, complementing the subcortical reflex readout from OptoDrum.

Evidence from the Literature

Kinuthia et al (2025) JCI Insight.
Zhang et al (2024) Exp Eye Res.
Zhang and colleagues provided the first systematic characterisation of tdTomato-induced retinal toxicity using OptoDrum as the functional readout, demonstrating that high-level tdTomato expression produces quantifiable optomotor deficits and RGC dysfunction. The study established that OptoDrum is sufficiently sensitive to detect reporter-gene-induced visual impairment before structural pathology is apparent, and defines expression-level thresholds relevant to gene therapy and reporter gene experimental design.
Garita-Hernandez et al, 2019
This review addresses the ocular safety considerations of optogenetic tools and viral vectors in retinal therapy research, providing the broader framework within which the reporter gene toxicity question raised by Zhang et al (2024) sits. Optomotor testing is identified as a suitable functional endpoint for ocular safety screening in vector-treated animals; Striatech’s OptoDrum delivers this endpoint in a fully automated, standardised format.
Vandenberghe et al, 2011
Vandenberghe et al established that AAV vector dose is a key determinant of retinal toxicity in primate gene therapy studies, documenting dose-dependent photoreceptor loss at high titres. While this study was conducted in primates with a custom assessment battery, the principle directly informs rodent vector safety studies in which OptoDrum provides the accessible, non-invasive functional readout for dose-response toxicity characterisation.

Can Visual Function Measurements Detect Mitochondrial and Metabolic Toxicity in Ocular and CNS Disease Models?

Audience A - Vision-focused

Audience B - CNS/Systemic

Quick Answer

Yes. Avrutsky et al (2022) demonstrated that OptoDrum-based visual acuity measurement detects progressive retinal degeneration in a mitochondrial complex I deficiency model, establishing the OMR as a non-invasive functional endpoint for metabolic toxicity affecting the visual system. Because mitochondrial complex I inhibitors such as rotenone and MPTP – standard neurotoxins in Parkinson’s disease research – use the same pathological mechanism as genetic complex I deficiency, these findings validate the OptoDrum as a functional biomarker of mitochondrial neurotoxicity relevant to the CNS pharmacology field as well as to dedicated retinal metabolism researchers.

The challenge

Retinal ganglion cells are among the most metabolically demanding neurons in the CNS, with energy requirements driven by their large cell bodies, long unmyelinated axons, and high firing rates. This metabolic vulnerability makes them acutely sensitive to mitochondrial toxicity: pharmacological inhibition of complex I (by rotenone or MPTP), complex II (by 3-nitropropionic acid), or complex III (by antimycin A) produces RGC degeneration in addition to the striatal and brainstem pathology typically characterised in neurotoxicology studies. Yet the functional retinal consequence of mitochondrial neurotoxin treatment is rarely measured in CNS toxicology studies, partly because dedicated ophthalmological assessment has historically required specialised equipment and expertise not routinely available in neuropharmacology laboratories.

The OptoDrum removes this barrier. Because the optomotor reflex is driven subcortically by the retina-to-brainstem projection – rather than cortically – it does not require cortical integrity to generate a valid measurement. This means that CNS researchers studying MPTP or rotenone neurotoxicity in motor and cognitive circuits can add an OptoDrum visual acuity measurement to their behavioural battery without any modification to their existing experimental protocol, obtaining a functional biomarker of retinal mitochondrial damage with four minutes of additional testing per animal. Avrutsky et al (2022) established this approach in a genetic complex I deficiency model, demonstrating that progressive optomotor acuity loss parallels retinal degeneration and can be tracked longitudinally in the same animals (Avrutsky et al, 2022, Transl Vis Sci Technol).

For CNS researchers, this connection has a further practical implication: if a candidate neuroprotective agent improves mitochondrial function in the brain, the same protection should manifest as preserved visual acuity in the same animal, providing a non-invasive, complementary functional endpoint that does not require additional brain tissue collection. For the disease context of rare inherited mitochondrial disorders, see the Rare and Inherited CNS and Eye Disorders application page and the Rare Disease cluster page.

How Striatech products help

Detects progressive visual acuity loss caused by mitochondrial toxicity to RGCs via non-invasive, automated OMR testing. Applicable in both pharmacological (rotenone, MPTP) and genetic (complex I subunit deletion) mitochondrial toxicity models. Provides a longitudinally repeatable functional endpoint compatible with standard CNS behavioural batteries.

ScotopicKit

When mitochondrial toxicity extends to photoreceptors or the outer retina (as in some complex I deficiency genotypes), scotopic OMR testing can detect rod-specific functional deficits earlier than photopic testing, providing a more complete metabolic toxicity profile of the retina.

Provides a cortically mediated, operant visual acuity endpoint for mitochondrial and metabolic toxicity models. Detects whether metabolic damage impairs learned visual discrimination and suprathreshold visual perception, complementing the subcortical reflex readout from OptoDrum and ScotopicKit.

Evidence from the Literature

Kinuthia et al (2025) JCI Insight.
Avrutsky et al (2022) Transl. Vis. Sci. Technol.
Avrutsky and colleagues applied a battery of non-invasive ophthalmological assessments, including OptoDrum-based visual acuity measurement, to a mouse model of mitochondrial complex I deficiency, demonstrating that progressive retinal degeneration is functionally detectable by the OMR and parallels structural changes quantified by OCT. The study validates OptoDrum as an accessible functional endpoint for metabolic retinal toxicity and bridges the rare genetic disease and pharmacological neurotoxin fields.
Lascaratos et al, 2007
Lascaratos and colleagues demonstrated that systemic mitochondrial efficiency correlates with RGC vulnerability to optic neuropathy, providing the mechanistic rationale for why mitochondrial toxins preferentially affect the optic nerve. This study used primate and histological endpoints; Striatech’s OptoDrum provides the non-invasive, in vivo functional equivalent for rodent mitochondrial toxicity studies.
Bhatt et al, 2014
This review establishes the conceptual and empirical basis for using retinal degeneration as a biomarker of mitochondrial disease severity, directly supporting the use of OptoDrum visual acuity as a non-invasive functional correlate of mitochondrial toxicity in both genetic and pharmacological paradigms.

How Can I Screen Candidate Drugs and Ocular Formulations for Tolerability and Efficacy in Toxicity Models?

Audience A - Vision-focused

Audience B - CNS/Systemic

Quick Answer

OptoDrum provides a non-invasive, high-throughput functional endpoint for both ocular drug safety (confirming that a formulation or delivery vehicle does not impair visual function) and efficacy (confirming that a candidate drug produces a functionally meaningful benefit in the retinal degeneration model being used). Pakian et al (2025) demonstrated this dual safety-and-efficacy role for a mucoadhesive topical ophthalmic formulation, using OptoDrum visual acuity as the in vivo functional readout in a retinal degeneration model.

The challenge

Preclinical ophthalmic drug development faces two parallel functional assessment requirements. The first is safety: novel drug candidates, excipients, preservatives, and novel delivery vehicles (including nanoparticles, polymeric carriers, and mucoadhesive matrices) must be demonstrated to be non-toxic to retinal function before they can advance to clinical development. The second is efficacy: in the retinal degeneration or toxicity model being used to evaluate the drug’s therapeutic potential, a functionally meaningful improvement in visual performance must be demonstrated alongside the structural or biochemical evidence of drug effect.

Both requirements call for the same instrument property: a quantitative, reproducible, in vivo functional endpoint that is sensitive to both deterioration (safety failure) and improvement (therapeutic efficacy). The OptoDrum fulfils both requirements through the same automated optomotor reflex paradigm, without requiring separate cohorts, terminal procedures, or ophthalmological specialist involvement. Because the OMR is mediated subcortically and is insensitive to sedation or cognitive state, it is particularly well-suited to pharmaceutical screening contexts where standardisation and reproducibility across large cohorts are paramount.

For researchers conducting preclinical safety pharmacology under regulatory guidance (ICH S8, ICH S7A/S7B), OptoDrum measurements can provide the non-clinical visual function safety data required by regulatory agencies, in an automated format that supports GLP-compatible data capture and reproducibility. For the broader context of retinal degeneration in preclinical drug evaluation, see the Retinal Degeneration and Inherited Retinal Disease application page.

How Striatech products help

Serves as both a safety screen (detecting drug- or excipient-induced visual toxicity) and an efficacy readout (confirming that a protective drug improves visual acuity in the toxicity model). Automated, observer-independent, and fully non-invasive; no training or anaesthesia required. Approximately 4 minutes per animal. Supports longitudinal, within-animal designs that reduce animal numbers required for dose-response studies.

Non-aversive Animal Platform

Provides a cortically mediated, operant visual acuity endpoint for drug and formulation tolerability screening. Confirms whether candidate compounds preserve learned visual discrimination and suprathreshold visual perception, complementing the subcortical reflex and refractive readouts from OptoDrum and Photorefractor.

Minimises handling-associated variability in large-cohort pharmaceutical screening studies, ensuring that between-group differences reflect genuine pharmacological effects rather than differential handling stress. Particularly relevant for aged or post-dosing animals that may be more sensitive to handling.

When the drug candidate targets the anterior segment, ciliary muscle, or lens (for example, anti-myopia compounds, anti-cataract agents, or ciliary muscle relaxants), Photorefractor provides the refractive endpoint to confirm that the drug’s mechanism of action is producing the expected optical effect without adverse refractive consequences.

Evidence from the Literature

Kinuthia et al (2025) JCI Insight.
Pakian et al (2025) Mol Pharm.
Pakian and colleagues used OptoDrum as an in vivo functional endpoint to evaluate both the tolerability of a novel mucoadhesive topical ocular drug delivery system and the efficacy of the delivered drug in a retinal degeneration model. The study demonstrates the dual safety-and-efficacy role of OptoDrum in ophthalmic pharmaceutical research, confirming that the formulation did not impair visual function and, where applicable, that the therapeutic compound produced a functionally meaningful benefit.

How Do Chemical Demyelination Models Relate to Toxic Optic Nerve Injury, and Which Visual Endpoints Apply?

Audience A - Vision-focused

Audience B - CNS/Systemic

Quick Answer

Chemical demyelination of the optic nerve – most commonly induced by lysophosphatidylcholine (LPC) injection – produces a toxic axon injury and RGC death cascade that is mechanistically distinct from immune-driven demyelination in EAE but that shares the optical nerve damage and visual acuity deficit as a common functional consequence. OptoDrum measures the degree of visual impairment and the extent of functional recovery after neuroprotective intervention in these models, as demonstrated by Baya Mdzomba et al (2020), who showed that Nogo-A antibody therapy promotes visual recovery after toxic optic nerve injury.

The challenge

Lysophosphatidylcholine (LPC) is a membrane-disrupting lipid that, when injected into white matter tracts including the optic nerve, produces local, reproducible, and well-demarcated demyelinating lesions. Unlike the diffuse, immune-mediated demyelination of EAE, LPC lesions are geographically controlled by the injection site, making them well-suited to mechanistic studies of axon damage, myelin repair, and the relationship between myelination status and axon survival. The toxicological relevance of LPC is that it models the direct lipotoxic component of demyelinating injury – the membrane damage caused by phospholipid disruption – independently of adaptive immune involvement.

When applied to the optic nerve, LPC produces a chemical optic neuropathy whose severity and recovery can be tracked using OptoDrum visual acuity measurement. The functional readout is particularly informative in intervention studies: because the primary injury is chemically defined and spatially limited, any improvement in optomotor performance following treatment can be attributed to the treatment effect on remyelination, axon protection, or RGC rescue rather than to modulation of systemic immune activity. Baya Mdzomba et al (2020) demonstrated this approach, using OptoDrum to confirm that Nogo-A antibody treatment produced a functionally meaningful gain in visual acuity after toxic optic nerve injury (Baya Mdzomba et al, 2020, Cell Death Dis).

Researchers working with chemical demyelination models should note the substantive overlap with the neuroinflammation and trauma fields: LPC demyelination co-activates microglia and peripheral immune cells (the neuroinflammatory arm) and produces mechanical axon damage at the injection site (the traumatic arm). For a broader perspective on the neuroinflammatory aspects, see the Neuroinflammation and Autoimmune CNS Disease application page and the Neuroinflammation cluster page. For the trauma and acute injury angle, including ONC and its overlap with demyelinating injury, see the Trauma and Acute Injury application page. For the optic nerve damage cluster and regeneration angle, see the Optic Nerve Damage and Optic Nerve Regeneration cluster pages. For the RGC death mechanisms in toxic demyelination, see the Retinal Ganglion Cell Death cluster page.

How Striatech products help

Measures visual acuity and contrast sensitivity as a functional indicator of optic nerve demyelination severity and remyelination/regeneration-mediated recovery. Non-invasive and repeatable, enabling longitudinal tracking of functional deficit and recovery trajectory in the same animal across the full injury-and-repair time course.

DOI: 10.1016/j.bcp.2026.117698 >>

Provides a cortically mediated, operant visual acuity endpoint for chemical demyelination and toxic optic nerve injury models. Assesses whether demyelination-driven visual pathway damage impairs learned visual discrimination, complementing the subcortical reflex readout from OptoDrum.

Evidence from the Literature

Kinuthia et al (2025) JCI Insight.
Baya Mdzomba et al (2020) Cell Death Dis.
Baya Mdzomba and colleagues demonstrated that anti-Nogo-A antibody treatment after toxic optic nerve injury promotes RGC survival and visual recovery, confirmed by OptoDrum-measured visual acuity as the primary functional endpoint. The study establishes OptoDrum as a valid readout for chemically-induced optic neuropathy and demonstrates its sensitivity to treatment-induced partial functional recovery. Given its primary relevance to axon biology and neuroprotection, this study is most comprehensively discussed on the Trauma and Acute Injury application page.
Blakemore and colleagues, 2008
This review establishes LPC and related toxin-induced demyelination models as the primary tools for studying myelin repair in the CNS, providing the scientific context for using visual endpoints in chemical demyelination studies of the optic nerve. The OMR-based visual acuity readout from OptoDrum is the appropriate functional endpoint for optic nerve demyelination experiments in this modelling paradigm.

Product Fit

Summary: Striatech Products supporting your research questions

Research Question	OptoDrum	ScotopicKit	AcuiSee	Photorefractor	Keratometer	DarkAdapt	Non-aversive Platform
Chemical toxin models (NaIO3, NMDA)	Yes	Yes	Yes			Yes (with ScotopicKit)
Ciliary / refractive toxicity				Yes	Yes
Reporter gene / viral vector toxicity	Yes		Yes
Mitochondrial / metabolic toxicity	Yes	Yes	Yes			Yes (with ScotopicKit)
Drug / formulation safety screening	Yes		Yes	Yes			Yes
Chemical demyelination / toxic optic neuropathy	Yes		Yes

Measurement Modalities

Measuring Functional Visual Outcomes in Ocular and CNS Toxicity Models: How Do Available Methods Compare?

The table below compares the Striatech functional assessment tools with other modalities routinely used in toxicological characterisation of ocular and CNS disease models. The comparison is intended to be honest about where each tool adds value and where it is complementary rather than superior to alternatives.

Modality	What It Measures	Invasiveness	Anesthesia	Longitudinal Repeatability	Automation	Training Required	3Rs Impact	Key Limitation in Toxicity Studies
OptoDrum (OMR)	Photopic visual acuity and contrast sensitivity; retina-to-brainstem pathway integrity	Non-invasive	No	Daily if needed; no upper limit	Fully automated	Minimal	Enables within-animal longitudinal designs; replaces terminal cohorts at many time points	Measures subcortical OMR only; does not assess outer retinal (photoreceptor) or cortical function directly
OptoDrum + ScotopicKit	Scotopic (rod-mediated) visual acuity and contrast sensitivity	Non-invasive	No	Daily if needed; dark-adaptation protocol required	Fully automated	Minimal; dark-adaptation protocol needed	As above; extends to outer retinal / rod-photoreceptor compartment	Dark adaptation adds ~30 min per experimental session
Photorefractor	Refractive state (diopters); anterior segment optical quality	Non-invasive	No	Yes; daily feasible	Automated	Minimal	Non-invasive; no surgical procedures needed	Measures refractive state only; does not assess visual acuity, retinal function, or IOP
Keratometer	Corneal radius of curvature; anterior corneal geometry	Non-invasive	No	Yes	Automated	Minimal	Non-invasive; complements Photorefractor	Measures corneal structure only; cannot detect sub-corneal or retinal changes
Flash ERG	Photoreceptor (a-wave) and inner retinal (b-wave) electrical responses; outer and inner retinal function	Minimally invasive (corneal electrode)	Yes (typically)	Limited by anaesthesia burden; typically weekly or less	Moderate	Moderate to high; electrophysiology expertise required	Provides outer retinal readout not captured by OMR; anaesthesia adds welfare burden	Anaesthesia introduces variability; cannot easily be combined with daily tracking protocols
Optical Coherence Tomography (OCT)	Retinal layer thickness; structural readout of RNFL, RGCL, outer nuclear layer	Non-invasive (mydriasis typically required)	Yes (typically, for immobilisation)	Weekly or biweekly feasible	Semi-automated (image acquisition and segmentation)	Moderate; image analysis expertise required	Provides structural rather than functional data; complements OMR	Structural endpoint only; does not confirm functional consequence of structural change
Histological cell counting (RPE counts, RGC counts)	Absolute surviving cell numbers; retinal flat-mount or section quantification	Terminal	Yes (terminal)	None (terminal)	Semi-automated (counting algorithms)	Moderate; immunohistochemistry expertise required	High 3Rs burden; requires separate cohorts at each time point	Cannot confirm functional consequence of cell loss; requires terminal procedure
Clinical scoring (body weight, neurological deficit, ophthalmic slit-lamp exam)	Gross neurological and ocular health status	Non-invasive to minimally invasive	Variable	Yes	Low (observer-dependent)	Moderate (inter-rater standardisation)	Widely used; low animal burden	Not quantitative; cannot detect subtle functional deficits in early toxicity stages

In most ocular and CNS toxicity studies, the optimal experimental design combines the OptoDrum (and Photorefractor where refractive endpoints are relevant) with at least one structural modality (OCT or histology) and, where feasible, ERG for outer retinal characterisation. The OptoDrum's specific contribution is the non-invasive, automated, longitudinally repeatable functional endpoint that bridges between structural assessment time points and eliminates the need for separate animal cohorts at each histological time point. For a detailed discussion of how Striatech instruments contribute to the 3Rs framework in visual neuroscience research, see the product pages at stria.tech.

Supported by Striatech Products

Publications on Ocular and CNS Toxicity Models

Biochemical Pharmacology (Mar 01, 2026) Quercetin ameliorates SIRT1-mediated oxidative stress and inflammation to attenuate ciliary muscle remodeling in experimental myopia

Yang Y, Zhang M, Zhang R, Wu M, Hao J, Ma Z, Yang Z, Zhang Y, Guo D, Bi H

Featured image for “Quercetin ameliorates SIRT1-mediated oxidative stress and inflammation to attenuate ciliary muscle remodeling in experimental myopia”

Quercetin attenuated lens‑induced myopia in guinea pigs by limiting axial elongation and refractive shift while improving ciliary muscle thickness and fiber organization. Mechanistically, treatment upregulated SIRT1, NRF2, and TIMP‑2, reduced KEAP1, MMP‑2, oxidative stress markers, and inflammatory cytokines, and partially restored mitochondrial membrane potential and calcium homeostasis, indicating protection against ciliary muscle remodeling.

This study aimed to investigate the role of quercetin in myopic ciliary muscle remodeling through the regulation of SIRT1 expression. To this end, a randomized controlled trial was conducted using negative lens-induced myopic (LIM) guinea pig models for durations of 4 weeks and 6 weeks, with subjects administered quercetin (QUE) or SRT1720. Changes in axial lengths and refractive errors were measured at 4 and 6 weeks. Subsequently, protein expression (e.g., SIRT1, KEAP1, NRF2, MMP-2, and TIMP-2) in ciliary muscles was analyzed by Western blotting, while the expression of inflammatory cytokines (e.g., TNF-α, IL-6, and IL-10) was quantified via ELISA, and ciliary muscle morphologies were assessed using hematoxylin and eosin (H&E) staining and optical coherence tomography (OCT). Calcium fluxes, reactive oxygen species (ROS) levels, and mitochondrial membrane potentials (ΔΨm) were measured via noninvasive microtests and flow cytometry. Compared with the LIM group, the QUE and SIRT1 activator (SRT1720) intervention groups presented significantly reduced axial elongation amounts and refractive errors (P < 0.01), along with thickened ciliary muscles and improved fiber alignments. Additionally, the calcium influx and ROS levels were significantly reduced, and the ΔΨm levels were partially restored. Furthermore, Western blotting revealed upregulated SIRT1, NRF2, and TIMP-2 expression but downregulated KEAP1 and MMP-2 expression in the intervention groups, and ELISA revealed decreased inflammatory responses. In conclusion,quercetin could play a protective role by increasing the expression of SIRT1, which in turn alleviated KEAP1/NRF2-induced oxidative stress and mitigated NF-κB-driven inflammatory damage, thereby ameliorating ciliary muscle remodeling and potentially delaying the progression of myopia.

Related Products:

DOI: 10.1167/iovs.67.1.61 >>

Applications:
Myopia
·
Myopia, Refractive Development and Eye Growth
·
Toxicity
>

Investigative Ophthalmology & Visual Science (Jan 05, 2026) Vitamin E Alleviates Oxidative Damage and Attenuates Ferroptosis Caused by Prolonged Contraction of the Ciliary Muscle by Activating ACOT7

Cao H, Wu J, Xiang Y, Gao X, Kou J, Cheng H, Tan Y, Wan W, Liang L, Kang J, Zheng S, Hu K

Featured image for “Vitamin E Alleviates Oxidative Damage and Attenuates Ferroptosis Caused by Prolonged Contraction of the Ciliary Muscle by Activating ACOT7”

The study found that prolonged contraction of the eye’s ciliary muscle damages its cells by increasing oxidative stress, disturbing iron balance, and triggering ferroptosis in guinea pigs and cultured cells. Striatech’s Photorefractor was used to track changes in refractive error over time, providing a functional measure of how well the eye could still focus. Vitamin E eye drops reduced these harmful changes and helped preserve ciliary muscle function, likely by activating the protective enzyme ACOT7.

Background: The ciliary muscle, a critical intraocular smooth muscle, plays a potent role in ocular accommodation. Investigating the potential detrimental effects on the ciliary muscle during prolonged contraction and precise mechanism underlying the cell damage hold significance in treating ciliary muscle dysfunction. The effect and mechanism of vitamin E (VitE), an antioxidant, in mitigating these adverse effects of prolonged contraction remains to be thoroughly elucidated. Methods: A guinea pig model of prolonged contraction of the ciliary muscle was established through topical administration of carbachol, and primary ciliary muscle cells isolated from guinea pigs were used for in vitro experiments. Results: The ophthalmic examination results demonstrated that prolonged contraction of the ciliary muscle impaired accommodative function in guinea pigs. This condition may lead to disrupted cellular migration, intracellular adenosine triphosphate depletion, decreased mitochondrial membrane potential, and reactive oxygen species accumulation. Further examination revealed that carbachol induced darker-stained mitochondrial membranes and diminished cristae density, consistent with morphological features of ferroptosis. Moreover, sustained cell contraction modulated specific contraction-related proteins (α-smooth muscle actin), concurrently decreased the expression of antioxidant proteins (glutathione peroxidase, superoxide dismutase, catalase, and GSH) in both tissue specimens and cells, culminating in ferroptosis in vivo and in vitro experiments. Our findings demonstrated that pretreatment with VitE alleviated oxidative injury and mitigated ferroptosis. Additionally, knocking down acetyl-coenzyme A thiosterase 7 attenuated the beneficial effect of VitE. Conclusions: These findings collectively indicated that VitE presented a viable approach to ameliorate oxidative stress and ferroptosis induced by prolonged contraction of the ciliary muscle via activating acetyl-coenzyme A thiosterase 7.

Related Products:

DOI: 10.1021/acs.molpharmaceut.5c00079 >>

Applications:
Myopia
·
Myopia, Refractive Development and Eye Growth
·
Toxicity
>

Molecular Pharmaceutics Journal (Apr 07, 2025) Topical Administration of Mucoadhesive Liposomes-Epoetin-β for Targeting the Ocular Posterior Segment

Pakian S, Nabid MR, Satarian L, Abandansari HS, Mirkani A

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This preclinical study developed topical mucoadhesive thiolated hyaluronic acid–modified cationic liposomes to deliver the neuroprotective agent Epoetin-β to the retinal posterior segment. The nanoformulation showed uniform size, good biocompatibility in RGC-5 cells, and achieved about 1.9-fold higher retinal penetration versus free Epoetin-β in mice, with a trend toward better visual acuity after optic nerve injury. Behavioral assessment using optomotor response relied on Striatech’s OptoDrum system, supporting sensitive detection of functional recovery.

Delivering drugs to the posterior eye segment is a complex task, particularly for treating retinal diseases. Neuroprotective approaches to maintain neuronal integrity have garnered significant attention in recent research. Here, we developed a mucoadhesive nanoparticulate system based on thiolated hyaluronic acid-modified cationic liposomes (HA-SH@liposomes) for topical administration. To fabricate these liposomes, we utilized microfluidic technology with a toroidal mixer to ensure consistent size and stability. Cationic liposomes were prepared by using the microfluidic method, and Epoetin-β (EPOβ), a neuroprotective agent, was loaded into the liposomes. Following this, HA-SH was conjugated to the EPOβ/HA-SH@liposomes using a postmicrofluidics conjugation method, wherein HA-SH was added dropwise to facilitate electrostatic interactions between the cationic liposomes and the anionic polymer. The resulting liposomes exhibited a mean size of 144 ± 1.3 nm and a polydispersity index (PDI) of 0.09 ± 0.01, indicating their uniformity. We evaluated the biocompatibility of the EPOβ/HA-SH@liposomes in vitro using live/dead and MTS assays on the RGC-5 cell line, demonstrating no notable cytotoxicity compared to the controls. To assess the in vivo performance, we conducted extensive ophthalmological examinations in C57/BL6 mice, including immunofluorescence staining to track the distribution of EPOβ and EPOβ/HA-SH@liposomes within the eyeball. Additionally, we quantified EPOβ levels in the retina using an enzyme-linked immunosorbent assay (ELISA) kit after the topical application of free EPOβ and the EPOβ/HA-SH@liposome formulation. The immunofluorescence staining revealed efficient delivery of EPOβ into the retina and choroid via the transcorneal route when administered as EPOβ/HA-SH@liposomes. ELISA results showed that the liposomal formulation achieved approximately 1.9× greater penetration efficiency than free EPOβ. Furthermore, optokinetic response (OKR) assays indicated that animals treated with EPOβ/HA-SH@liposomes exhibited slightly improved visual acuity compared with those treated with free EPOβ, though the difference was not statistically significant. In conclusion, the topical ocular administration of EPOβ/HA-SH@liposomes facilitated the efficient delivery of EPOβ to the retina, promoting retinal recovery and confirming its neuroprotective properties. This preclinical study provides a foundation for innovative strategies in the topical delivery of neuroprotective agents in ocular therapy.

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DOI: 10.1016/j.phymed.2024.155982 >>

Applications:
Ocular and CNS Toxicity Models
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Retinal Degeneration
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Retinal Degeneration and Inherited Retinal Disease
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Phytomedicine (Nov 01, 2024) Lutein protects senescent ciliary muscle against oxidative stress through the Keap1/Nrf2/ARE pathway

Gao N, Gao X, Du M, Xiang Y, Zuo H, Huang R, Wan W, Hu K

Featured image for “Lutein protects senescent ciliary muscle against oxidative stress through the Keap1/Nrf2/ARE pathway”

This research explored how lutein, a plant nutrient found in leafy greens, might help the aging muscles in the eye that control focusing (the ciliary muscle). In older guinea pigs, lutein reduced harmful oxidative stress in the ciliary muscle, improved its ability to help the eye change focus, and lowered age-related changes in vision. The protective effect appears to work through a cellular antioxidant system known as the Keap1/Nrf2/ARE pathway, which helps cells defend against damage. In lab-grown muscle cells, lutein also reduced signs of aging and boosted protective proteins, suggesting it could help maintain eye focusing function as people age. Striatech’s Photorefractor measured refractive state and accommodative response, enabling evaluation of lutein’s effects on age-related visual function.

Background: Aging-induced decline in ciliary muscle function is an important factor in visual accommodative deficits in elderly adults. With this study, we provide an innovative investigation of the interaction between ciliary muscle aging and oxidative stress. Methods: Tricolor guinea pigs were used for the experiments in vivo and primary guinea pig ciliary smooth muscle cells were used for the experiments in vitro.Results: We enriched for genes associated with muscle-aging-lutein relationship using bioinformatics, including Nuclear factor-erythroid 2-related factor-2 (Nrf2), Glutathione Peroxidase (GPx) gene family, Superoxide Dismutase (SOD) gene family, NAD(P)H: Quinone Oxidoreductase 1 (NQO1) and Heme Oxygenase-1 (HO-1). After gavage to aged guinea pigs, lutein reduced Reactive Oxygen Species (ROS) and P21 levels in senescent ciliary muscle; lutein decreased refractive error and restored accommodation of the eye. In addition, lutein increased GPx, SOD, and Catalase (CAT) levels in serum; lutein increased GPx and CAT levels in ciliary bodies. Lutein regulated the expression of proteins such as Nrf2, Kelch-like ECH-associated protein 1 (Keap1), and downstream proteins in senescent ciliary bodies. Similarly, guinea pig ciliary muscle cell senescence was associated with oxidative stress. In vitro, 100 μM lutein reversed the damage caused by 800 μM H2O2; it reduced Senescence-Associated β-galactosidase (SA-β-Gal) and ROS activites, cell apoptosis and cell migration. Also, lutein increased the expression of smooth muscle contractile proteins. Lutein also increased the expression of Nrf2, GPx2, NQO1 and HO-1, decreased the expression of Keap1. A reduction in Nrf2 activity led to a reduction in the ability of lutein to activate antioxidant enzymes in the cells, thus reducing its inhibitory effect on cell senescence. Conclusion: lutein improved resistance to oxidative stress in senescent ciliary muscle in vivo and in vitro by regulating the Keap1/Nrf2/Antioxidant Response Element pathway. We have innovatively demonstrated the molecular pharmacological mechanism by which lutein reverse age-related ciliary muscle systolic and diastolic deficits.

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DOI: 10.1096/fj.202401286R >>

Applications:
Aging
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Myopia, Refractive Development and Eye Growth
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Ocular and CNS Toxicity Models
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Systemic Aging and CNS decline
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Toxicity
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The FASEB Journal (Aug 15, 2024) Pilocarpine mediated excessive calcium accumulation leads to ciliary muscle cell senescence and apoptosis

Gao X, Gao N, Du M, Xiang Y, Zuo H, Cao H, Zheng S, Huang R, Wan W, Hu K

Featured image for “Pilocarpine mediated excessive calcium accumulation leads to ciliary muscle cell senescence and apoptosis”

Researchers studied what happens when the eye’s focusing muscle (the ciliary muscle) is overstimulated using a drug called pilocarpine in guinea pigs. They measured changes in refraction, using Striatech’s photorefractor. While the overall shape of the eye did not change significantly, the muscle’s ability to adjust focus became impaired. Overstimulation caused harmful changes inside muscle cells, including increased oxidative stress, excess calcium buildup, and damage to mitochondria, leading to cell aging and death. The findings suggest that controlling calcium levels may help protect the eye’s focusing ability.

The ciliary muscle constitutes a crucial element in refractive regulation. Investigating the pathophysiological mechanisms within the ciliary muscle during excessive contraction holds significance in treating ciliary muscle dysfunction. A guinea pig model of excessive contraction of the ciliary muscle induced by drops pilocarpine was employed, alongside the primary ciliary muscle cells was employed in in vitro experiments. The results of the ophthalmic examination showed that pilocarpine did not significantly change refraction and axial length during the experiment, but had adverse effects on the regulatory power of the ciliary muscle. The current data reveal notable alterations in the expression profiles of hypoxia inducible factor 1 (HIF-1α), ATP2A2, P53, α-SMA, Caspase-3, and BAX within the ciliary muscle of animals subjected to pilocarpine exposure, alongside corresponding changes observed in cultured cells treated with pilocarpine. Augmented levels of ROS were detected in both tissue specimens and cells, culminating in a significant increase in cell apoptosis in in vivo and in vitro experiments. Further examination revealed that pilocarpine induced an increase in intracellular Ca²⁺ levels and disrupted MMP, as evidenced by mitochondrial swelling and diminished cristae density compared to control conditions, concomitant with a noteworthy decline in antioxidant enzyme activity. However, subsequent blockade of Ca²⁺ channels in cells resulted in downregulation of HIF-1α, ATP2A2, P53, α-SMA, Caspase-3, and BAX expression, alongside ameliorated mitochondrial function and morphology. The inhibition of Ca²⁺ channels presents a viable approach to mitigate ciliary cells damage and sustain proper ciliary muscle function by curtailing the mitochondrial damage induced by excessive contractions.

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DOI: 10.1016/j.exer.2024.109910 >>

Applications:
Myopia, Refractive Development and Eye Growth
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Ocular and CNS Toxicity Models
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Toxicity
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Experimental Eye Research (Apr 24, 2024) Effects of fluorescent protein tdTomato on mouse retina

Zhang CJ, Mou H, Yuan J, Wang YH, Sun SN, Wang W, Xu ZH, Yu SJ, Jin K, Jin ZB

The authors showed that expression of tdTomato in transgenic mice causes retinal dysfunction: photopic ERG responses are reduced, and contrast sensitivity is impaired, as demonstarted with Striatech’s OptoDrum. The cause appears to be mitochondrial disfunction associated with ultrastructural abnormalities. These findings indicate that tdTomato can adversely affect retinal neuronal function.

Fluorescent proteins (FPs) have been widely used to investigate cellular and molecular interactions and trace biological events in many applications. Some of the FPs have been demonstrated to cause undesirable cellular damage by light-induced ROS production in vivo or in vitro. However, it remains unknown if one of the most popular FPs, tdTomato, has similar effects in neuronal cells. In this study, we discovered that tdTomato expression led to unexpected retinal dysfunction and ultrastructural defects in the transgenic mouse retina. The retinal dysfunction mainly manifested in the reduced photopic electroretinogram (ERG) responses and decreased contrast sensitivity in visual acuity, caused by mitochondrial damages characterized with cellular redistribution, morphological modifications and molecular profiling alterations. Taken together, our findings for the first time demonstrated the retinal dysfunction and ultrastructural defects in the retinas of tdTomato-transgenic mice, calling for a more careful design and interpretation of experiments involved in FPs.

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DOI: 10.1167/tvst.11.8.5 >>

Translational Vision Science & Technology (Aug 01, 2022) Noninvasive Ophthalmic Imaging Measures Retinal Degeneration and Vision Deficits in Ndufs4^−/− Mouse Model of Mitochondrial Complex I Deficiency

Avrutsky MI, Lawson JM, Smart JE, Chen CW, Troy CM

Featured image for “Noninvasive Ophthalmic Imaging Measures Retinal Degeneration and Vision Deficits in Ndufs4−/− Mouse Model of Mitochondrial Complex I Deficiency”

Mitochondrial complex I disorders are a heterogeneous group of rare inherited diseases caused by mutations affecting proteins in the mitochondrial electron transport chain. Neurological and ophthalmic pathologies are common to many forms of complex I deficiency, due to the high energy demands of central nervous system tissues. Avrutsky et al characterized one such mouse model, carrying a mutation in Ndufs4 (NADH:ubiquinone oxidoreductase Fe-S protein 4), which shows fast retinal degeneration within only a few weeks. They show that a range of non-invasive techniques (OCT for structural changes, ERG for electrophysiological properties, and OMR with our OptoDrum for behavioral assessment) can capture relevant measures of disease progression.

Purpose: To characterize postnatal ocular pathology in a Ndufs4^−/− mouse model of complex I deficiency using noninvasive retinal imaging and visual testing. Methods: Ndufs4^−/− mice and wild-type (WT) littermates were analyzed at 3, 5, and 7 weeks postnatal. Retinal morphology was visualized by optical coherence tomography (OCT). OCT images were analyzed for changes in retinal thickness and reflectivity profiles. Visual function was assessed by electroretinogram (ERG) and optomotor reflex (OMR). Results: Ndufs4^−/− animals have normal OCT morphology at weaning and develop inner plexiform layer atrophy over weeks 5 to 7. Outer retinal layers show hyporeflectivity of the external limiting membrane (ELM) and photoreceptor ellipsoid zone (EZ). Retinal function is impaired at 3 weeks, with profound deficits in b-wave, a-wave, and oscillatory potential amplitudes. The b-wave and oscillatory potential implicit times are delayed, but the a-wave implicit time is unaffected. Ndufs4^−/− animals have normal OMR at 3 weeks and present with increasing acuity and contrast OMR deficits at 5 and 7 weeks. Physiological thinning of inner retinal layers, attenuation of ELM reflectivity, and attenuation of ERG b- and a-wave amplitudes occur in WT C57BL/6 littermates between weeks 3 and 7. Conclusions: Noninvasive ocular imaging captures early-onset retinal degeneration in Ndufs4^−/− mice and is a tractable approach for investigating retinal pathology subsequent to complex I deficiency. Translational relevance: Ophthalmic imaging captures clinically relevant measures of retinal disease in a fast-progressing mouse model of complex I deficiency consistent with human Leigh syndrome.

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DOI: 10.1038/s41419-020-2302-x >>

Applications:
Ocular and CNS Toxicity Models
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Rare and Inherited CNS and Eye Disorders
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Rare Disease
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Retinal Degeneration
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Cell Death & Disease (Feb 06, 2020) Nogo-A-targeting antibody promotes visual recovery and inhibits neuroinflammation after retinal injury

Baya Mdzomba J, Joly S, Rodriguez L, Dirani A, Lassiaz P, Behar-Cohen F, Pernet V

Journal Club

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Nogo-A is a potent myelin-associated inhibitor of neuronal growth and nervous system plasticity. It may be involved in many ocular diseases by preventing healing and recovery after physiological insults. This study shows that antibodies directed against Nogo-A promoted recovery after retinal injury. Baya Mdzomba et al monitor the visual acuity of the treated mice with our OptoDrum which provided a non-invasive readout of the injury and recovery, and enabled the researchers to get daily measurements of disease progression.

N-Methyl-D-aspartate (NMDA)-induced neuronal cell death is involved in a large spectrum of diseases affecting the brain and the retina such as Alzheimer’s disease and diabetic retinopathy. Associated neurological impairments may result from the inhibition of neuronal plasticity by Nogo-A. The objective of the current study was to determine the contribution of Nogo-A to NMDA excitotoxicity in the mouse retina. We observed that Nogo-A is upregulated in the mouse vitreous during NMDA-induced inflammation. Intraocular injection of a function-blocking antibody specific to Nogo-A (11C7) was carried out 2 days after NMDA-induced injury. This treatment significantly enhanced visual function recovery in injured animals. Strikingly, the expression of potent pro-inflammatory molecules was downregulated by 11C7, among which TNFα was the most durably decreased cytokine in microglia/macrophages. Additional analyses suggest that TNFα downregulation may stem from cofilin inactivation in microglia/macrophages. 11C7 also limited gliosis presumably via P.Stat3 downregulation. Diabetic retinopathy was associated with increased levels of Nogo-A in the eyes of donors. In summary, our results reveal that Nogo-A-targeting antibody can stimulate visual recovery after retinal injury and that Nogo-A is a potent modulator of excitotoxicity-induced neuroinflammation. These data may be used to design treatments against inflammatory eye diseases.

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DOI: 10.1167/iovs.14-14325 >>

Investigative Ophthalmology & Visual Science (Aug 07, 2014) Characterization of a mouse model with complete RPE loss and its use for RPE cell transplantation

Carido M, Zhu Y, Postel K, Benkner B, Cimalla P, Karl MO, Kurth T, Paquet-Durand F, Koch E, Münch TA, Tanaka EM, Ader M

Featured image for “Characterization of a mouse model with complete RPE loss and its use for RPE cell transplantation”

Carido et al present the sodium iodate mouse model of age-related macular degeneration. Systemic injection of sodium iodate leads to death of retinal pigment epithelium, with subsequent photoreceptor cell death. OptoDrum measurements show that the vision loss can be tracked at the behavioral level.

Purpose: Age-related macular degeneration (AMD) is a major leading cause of visual impairment and blindness with no cure currently established. Cell replacement of RPE is discussed as a potential therapy for AMD. Previous studies were performed in animal models with severe limitations in recapitulating the disease progression. In detail, we describe the effect of systemic injection of sodium iodate in the mouse retina. We further evaluate the useful-ness of this animal model to analyze cell-specific effects following transplantation of human embryonic stem cell (hESC)-derived RPE cells. Methods: Morphologic, functional, and behavioral changes following sodium iodate injection were monitored by histology, gene expression analysis, electroretinography, and optokinetic head tracking. Human embryonic stem cell–derived RPE cells were transplanted 1 week after sodium iodate injection and experimental retinae were ana-lyzed 3 weeks later. Results: Injection of sodium iodate caused complete RPE cell loss, photoreceptor degeneration, and altered gene and protein expression in outer and inner nuclear layers. Retinal function was severely affected by day 3 and abol-ished from day 14. Following transplantation, donor hESC-derived RPE cells formed extensive monolayers that dis-played wild-type RPE cell morphology, organization, and function, including phagocytosis of host photoreceptor outer segments. Conclusions: Systemic injection of sodium iodate has considerable effects on RPE, photoreceptors, and inner nu-clear layer neurons, and provides a model to assay reconstitution and maturation of RPE cell transplants. The avail-ability of an RPE-free Bruch's membrane in this model likely allows the unprecedented formation of extensive polar-ized cell monolayers from donor hESC-derived RPE cell suspensions.

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