Is sex a biological variable in corneal wound healing?

Tripathi, Ratnakar; Giuliano, Elizabeth A.; Gafen, Hannah B.; Gupta, Suneel; Martin, Lynn M.; Sinha, Prashant R.; Rodier, Jason T.; Fink, Michael; Hesemann, Nathan P.; Chaurasia, Shyam S.; Mohan, Rajiv R.

doi:10.1016/j.exer.2019.107705

Cited by 21 publications

(22 citation statements)

References 52 publications

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“…The rabbit eye was chosen because of its similarity in size and anatomical features to the human eye in terms of dimensions, cellular composition, and physiological properties, except for the absence of the Bowman's layer. Furthermore, corneal wound healing events in rabbit eyes are similar to those in human eyes 16–18 . We found that topical or vapor application of acrolein severely damages the rabbit eye and causes a battery of ocular pathologies, including swelling of the eye, ocular surface abnormalities, inflammation, irregular collagen accumulation, and corneal opacity.…”

Section: Introductionmentioning

confidence: 70%

“…We selected the seven most relevant time points (30 min and 1, 3, 7, 14, 21, and 28 days) based on our previously published data on corneal wound healing. 17,18,22,23,26 We optimized two different modes of exposure (vapor and topical) that represent real-world situations. Next, we standardized two different times of exposure (1 and 3 min for vapor exposure and 1 and 5 min for topical exposure) and its effect on ocular damage and vision loss.…”

Section: Discussionmentioning

confidence: 99%

“…This observation is consistent with our previous report that showed that sex is not a biological variable in corneal wound healing in the rabbit model. 17 A single exposure to acrolein by vapor or topically caused a massive wave of anterior segment trauma within 30 minutes. The clinical parameters observed include inflamed and swollen eyelids (also known as blepharitis), a significant spike in the IOP in the eyes of the 1-min vapor exposure group lasting until day 7 and until day 14 in the 3-min vapor exposure group, excessive tear volume, and corneal edema.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, corneal wound healing events in rabbit eyes are similar to those in human eyes. [16][17][18] We found that topical or vapor application of acrolein severely damages the rabbit eye and causes a battery of ocular pathologies, including swelling of the eye, ocular surface abnormalities, inflammation, irregular collagen accumulation, and corneal opacity. In summary, we have established an in vivo rabbit model for studying acrolein toxicity to the eye.…”

Section: Introductionmentioning

confidence: 99%

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A rabbit model for evaluating ocular damage from acrolein toxicity in vivo

Gupta

Fink

Martin

et al. 2020

Annals of the New York Academy of Sciences

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Acrolein is a highly reactive and volatile unsaturated aldehyde commonly used for producing scores of commercial products. It has been recognized as a chemical weapon since its use during World War I, and more recently, in Syria. Acrolein exposure causes severe eye, skin, and lung damage in addition to many casualties. In the eye, it causes severe pain, eyelid swelling, corneal burns, and vision impairment. Very little information is available about how acrolein damages the cornea and causes vision loss. At present, the lack of clinically relevant animal models limits evaluation of acrolein toxicity and mechanisms specific to the eye. We aim to standardize the mode of delivery and exposure duration of acrolein, damaging the rabbit eye in vivo as an ocular injury model for studying the toxicity of acrolein and developing medical countermeasures. Rabbit eyes were exposed to two modes of delivery (topical and vapor) for different durations (1-5 minutes). Clinical ophthalmic examinations with a slit lamp, stereomicroscope, fluorescein dye, pachymeter, tonometer, and tearing examinations in live rabbits were performed at various times up to 4 weeks. Corneas were histologically diagnosed for transparency, fibrosis, collagens, and neovascularization. Our study successfully established an in vivo rabbit model for evaluating acrolein toxicity to the eye, accounting for different modes and durations of exposure.

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Section: Introductionmentioning

confidence: 70%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A rabbit model for evaluating ocular damage from acrolein toxicity in vivo

Gupta

Fink

Martin

et al. 2020

Annals of the New York Academy of Sciences

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“…We used 12 female New Zealand White rabbits 87 (Charles River), each 12–15 weeks old and weighing 2.5–3.0 kg. The Institutional Animal Care and Use Committee of SUNY Upstate Medical University approved the study.…”

Section: Methodsmentioning

confidence: 99%

USP10 Targeted Self-Deliverable siRNA to Prevent Scarring in the Cornea

Boumil

Castro

Phillips

et al. 2020

Molecular Therapy - Nucleic Acids

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Ocular scarring after surgery, trauma, or infection leads to vision loss. The transparent cornea is an excellent model system to test anti-scarring therapies. Cholesterol-conjugated fully modified asymmetric small interfering RNAs (siRNAs) (selfdeliverable siRNAs [sdRNAs]) are a novel modality for in vivo gene knockdown, transfecting cells and tissues without any additional formulations. Myofibroblasts are a main contributor to scarring and fibrosis. a v integrins play a central role in myofibroblast pathological adhesion, overcontraction, and transforming growth factor b (TGF-b) activation. Previously, we demonstrated that a v integrins are protected from intracellular degradation after wounding by upregulation of the deubiquitinase (DUB) ubiquitin-specific protease 10 (USP10), leading to integrin cell surface accumulation. In this study, we tested whether knockdown of USP10 with a USP10-targeting sdRNA (termed US09) will reduce scarring after wounding a rabbit cornea in vivo. The wounded corneal stroma was treated once with US09 or non-targeting control (NTC) sdRNA. At 6 weeks US09 treatment resulted in faster wound closure, limited scarring, and suppression of fibrotic markers and immune response. Specifically, fibronectin-extra domain A (EDA), collagen III, and a-smooth muscle actin (p < 0.05), CD45 + cell infiltration (p < 0.01), and apoptosis at 24 (p < 0.01) and 48 h (p < 0.05) were reduced post-wounding. Corneal thickness and cell proliferation were restored to unwounded parameters. Targeting the DUB, USP10 is a novel strategy to reduce scarring. This study indicates that ubiquitin-mediated pathways should be considered in the pathogenesis of fibrotic healing.

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Animal Models for Limbal Stem Cell Deficiency: A Critical Narrative Literature Review

Atalay,

Altuğ,

Çalışkan

et al. 2024

Ophthalmol Ther

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This literature review will provide a critical narrative overview of the highlights and potential pitfalls of the reported animal models for limbal stem cell deficiency (LSCD) and will identify the neglected aspects of this research area. There exists significant heterogeneity in the literature regarding the methodology used to create the model and the predefined duration after the insult when the model is supposedly fully fit for evaluations and/or for testing various therapeutic interventions. The literature is

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Is sex a biological variable in corneal wound healing?

Cited by 21 publications

References 52 publications

A rabbit model for evaluating ocular damage from acrolein toxicity in vivo

A rabbit model for evaluating ocular damage from acrolein toxicity in vivo

USP10 Targeted Self-Deliverable siRNA to Prevent Scarring in the Cornea

Animal Models for Limbal Stem Cell Deficiency: A Critical Narrative Literature Review

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