Corneal neuroepithelial compartmentalized microfluidic chip model for evaluation of toxicity-induced dry eye

Bonneau, Noémie; Potey, Anaïs; Vitoux, Michael-Adrien; Magny, Romain; Guerin, Camille; Baudouin, Christophe; Peyrin, Jean-Michel; Brignole-Baudouin, Françoise; Réaux-Le Goazigo, Annabelle

doi:10.1016/j.jtos.2023.11.004

Cited by 4 publications

(8 citation statements)

References 68 publications

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“…The most common manifestation of ocular surface toxic exposure is dry eye disease [ 30 , 31 ]. The public workshop series hosted by the National Academies of Sciences, Engineering, and Medicine in November 2023 named the health research priorities for the East Palestine hazardous materials’ release and named eye irritation as a commonly reported symptom [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

An Assessment of the Ocular Toxicity of Two Major Sources of Environmental Exposure

Rauchman,

Kasselman,

Srivastava

et al. 2024

IJERPH

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The effect of airborne exposure on the eye surface is an area in need of exploration, particularly in light of the increasing number of incidents occurring in both civilian and military settings. In this study, in silico methods based on a platform comprising a portfolio of software applications and a technology ecosystem are used to test potential surface ocular toxicity in data presented from Iraqi burn pits and the East Palestine, Ohio, train derailment. The purpose of this analysis is to gain a better understanding of the long-term impact of such an exposure to the ocular surface and the manifestation of surface irritation, including dry eye disease. In silico methods were used to determine ocular irritation to chemical compounds. A list of such chemicals was introduced from a number of publicly available sources for burn pits and train derailment. The results demonstrated high ocular irritation scores for some chemicals present in these exposure events. Such an analysis is designed to provide guidance related to the needed ophthalmologic care and follow-up in individuals who have been in proximity to burn pits or the train derailment and those who will experience future toxic exposure.

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Section: Discussionmentioning

confidence: 99%

An Assessment of the Ocular Toxicity of Two Major Sources of Environmental Exposure

Rauchman,

Kasselman,

Srivastava

et al. 2024

IJERPH

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“…Microfluidic chips were designed and manufactured, with the base and curing agent according to the manufacturing protocol of the polydimethylsiloxane (PDMS) chip as previously described ( Paul et al, 2011 ; Courte et al, 2018 ; Bonneau et al, 2023 ). Briefly, after PDMS chip demolding, cell seeding inlets were designed by punching 1 mm diameter inlets in each microfluidic chamber near the microchannel structures ( Figure 1 ).…”

Section: Methodsmentioning

confidence: 99%

“…TG cell suspension and seeding in microfluidic PDMS chips was performed as previously described ( Bonneau et al, 2023 ). Briefly, a total of 28 mice were euthanized by CO 2 inhalation followed by cervical dislocation.…”

Section: Methodsmentioning

confidence: 99%

“…As previously described ( Bonneau et al, 2023 ), CQ1, a confocal quantitative image cytometer (Yokogawa) was used to acquire images of the chips and perform 3D high-content quantitative analysis using system-provided algorithms CellpathFinder™ Software (Yokogawa). Briefly, a 3D analysis workflow was created for each type of immunostaining for the proximal and distal compartment separately.…”

Section: Methodsmentioning

confidence: 99%

“…Indeed, only one recent study presented compartmentalized models of primary sensory neurons from dorsal root ganglia (DRG) exposed either to inflammatory mediators (mimicking inflammatory peripheral sensitization) or paclitaxel (chemotherapy sensitization) ( Giorgi et al, 2023 ). We recently developed and validated a microfluidic co-culture between mouse trigeminal sensory neurons (responsible for corneal innervation) and primary mouse corneal epithelial cells to evaluate direct toxicity on nerve endings entangled in epithelial cells and indirect toxicity on somas after acute and repeated exposure to benzalkonium chloride, a commonly used preservative in eyedrops ( Bonneau et al, 2023 ). Such microfluidic device allowing a compartmentalization of TG neurons was then considered adequate for investigating trigeminal nerve regeneration after axotomy.…”

Section: Introductionmentioning

confidence: 99%

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Assessment of corneal nerve regeneration after axotomy in a compartmentalized microfluidic chip model with automated 3D high resolution live-imaging

Bonneau,

Potey,

Blond

et al. 2024

Front. Cell. Neurosci.

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IntroductionDamage to the corneal nerves can result in discomfort and chronic pain, profoundly impacting the quality of life of patients. Development of novel in vitro method is crucial to better understand corneal nerve regeneration and to find new treatments for the patients. Existing in vitro models often overlook the physiology of primary sensory neurons, for which the soma is separated from the nerve endings.MethodsTo overcome this limitation, our novel model combines a compartmentalized microfluidic culture of trigeminal ganglion neurons from adult mice with live–imaging and automated 3D image analysis offering robust way to assess axonal regrowth after axotomy.ResultsPhysical axotomy performed by a two-second aspiration led to a reproducible 70% axonal loss and altered the phenotype of the neurons, increasing the number of substance P-positive neurons 72 h post-axotomy. To validate our new model, we investigated axonal regeneration after exposure to pharmacological compounds. We selected various targets known to enhance or inhibit axonal regrowth and analyzed their basal expression in trigeminal ganglion cells by scRNAseq. NGF/GDNF, insulin, and Dooku-1 (Piezo1 antagonist) enhanced regrowth by 81, 74 and 157%, respectively, while Yoda-1 (Piezo1 agonist) had no effect. Furthermore, SARM1-IN-2 (Sarm1 inhibitor) inhibited axonal regrowth, leading to only 6% regrowth after 72 h of exposure (versus 34% regrowth without any compound).DiscussionCombining compartmentalized trigeminal neuronal culture with advanced imaging and analysis allowed a thorough evaluation of the extent of the axotomy and subsequent axonal regrowth. This innovative approach holds great promise for advancing our understanding of corneal nerve injuries and regeneration and ultimately improving the quality of life for patients suffering from sensory abnormalities, and related conditions.

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Advances in Ophthalmic Organ-on-a-Chip Models: Bridging Translational Gaps in Disease Modeling and Drug Screening

2024

IJTM

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Background: Organ-on-a-chip models have emerged as transformative tools in ophthalmology, offering physiologically relevant platforms for studying ocular diseases and testing therapeutic interventions. These microfluidic devices replicate human eye tissue architecture, addressing limitations of traditional in vitro and animal models. Methods: A narrative review of recent advancements in organ-on-a-chip technology was conducted, focusing on models simulating ocular structures like the retina and cornea and their applications in studying diseases such as dry eye disease (DED), age-related macular degeneration (AMD), and glaucoma. Results: Advanced organ-on-a-chip models successfully mimic key ocular features, providing insights into disease mechanisms and therapeutic responses. Innovations in microengineering and cellular integration have enhanced these platforms’ translational potential, though challenges like scalability and regulatory validation persist. Conclusions: Organ-on-a-chip models are poised to enhance preclinical research and clinical applications in ophthalmology. Addressing scalability and regulatory hurdles will be key to unlocking their full potential in drug discovery and disease modeling.

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Corneal neuroepithelial compartmentalized microfluidic chip model for evaluation of toxicity-induced dry eye

Cited by 4 publications

References 68 publications

An Assessment of the Ocular Toxicity of Two Major Sources of Environmental Exposure

An Assessment of the Ocular Toxicity of Two Major Sources of Environmental Exposure

Assessment of corneal nerve regeneration after axotomy in a compartmentalized microfluidic chip model with automated 3D high resolution live-imaging

Advances in Ophthalmic Organ-on-a-Chip Models: Bridging Translational Gaps in Disease Modeling and Drug Screening

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