Structural, Morphological, and Functional Correlates of Corneal Endothelial Toxicity Following Corneal Exposure to Sulfur Mustard Vapor

McNutt, Patrick; Tuznik, Kaylie; Nelson, Marian; Adkins, Angie; Lyman, Megan; Glotfelty, Elliot J.; Hughes, James E. O.; Hamilton, Tracey A.

doi:10.1167/iovs.13-12402

Cited by 35 publications

(33 citation statements)

References 27 publications

(48 reference statements)

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“…LEW at both 2.5 and 7.5 min exposure durations caused swelling and redness of the conjunctiva and iris, which resolved simultaneously at 4-14 days post-exposure; these injuries have been reported with both LEW and SM (10, 15, 22). Importantly, though the gross features of LEW-induced ocular injury in the present study in rabbits were observed within 6 h post-exposure, these lesions in rabbits including corneal injuries were observed 24-48 h post SM exposure (21, 25). However, similar to SM exposure, the severity of the clinical lesions including conjunctival edema, corneal opacity, corneal-stromal injury with LEW also peaked 24-72 h post-exposure (23, 26).…”

Section: Discussioncontrasting

confidence: 50%

Clinical progression of ocular injury following arsenical vesicant lewisite exposure

Tewari‐Singh

Croutch

Tuttle

et al. 2016

Cutaneous and Ocular Toxicology

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Ocular injury by lewisite (LEW), a potential chemical warfare and terrorist agent, results in edema of eyelids, inflammation, massive corneal necrosis, and blindness. To enable screening of effective therapeutics to treat ocular injury from LEW, useful clinically-relevant endpoints are essential. Hence, we designed an efficient exposure system capable of exposing up to six New-Zealand white rabbits at one time, and assessed LEW vapor-induced progression of clinical ocular lesions mainly in the cornea. The right eye of each rabbit was exposed to LEW (0.2 mg/L) vapor for 2.5, 5.0, 7.5 and 10.0 min and clinical progression of injury was observed for 28 days post-exposure (dose-response study), or exposed to same LEW dose for 2.5 and 7.5 min and clinical progression of injury was observed for up to 56 days post-exposure (time-response study); left eye served as an unexposed control. Increasing LEW exposure caused corneal opacity within 6 h post-exposure, which increased up to 3 days, slightly reduced thereafter till 3 weeks, and again increased thereafter. LEW-induced corneal ulceration peaked at 1 day post-exposure and its increase thereafter was observed in phases. LEW exposure induced neovascularization starting at 7 days which peaked at 22-35 days post-exposure, and remained persistent thereafter. In addition, LEW exposure caused corneal thickness, iris redness, and redness and swelling of the conjunctiva. Together, these findings provide clinical sequelae of ocular injury following LEW exposure and for the first time establish clinically-relevant quantitative endpoints, to enable the further identification of histopathological and molecular events involved in LEW-induced ocular injury.

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Section: Discussioncontrasting

confidence: 50%

Clinical progression of ocular injury following arsenical vesicant lewisite exposure

Tewari‐Singh

Croutch

Tuttle

et al. 2016

Cutaneous and Ocular Toxicology

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“…A weak positive correlation between severity of ocular and pulmonary involvement was found in a study of 292 Iran-Iraq conflict veterans (Ghasemi et al, 2012). McNutt et al (2013) provided insight into the progression and pathophysiological correlates for this injury.…”

Section: Sulfur Mustardmentioning

confidence: 99%

Mustards and Vesicants

Young¹,

Bast²

2015

Handbook of Toxicology of Chemical Warfare Agents

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“…While early therapeutic approaches have focused on preventing epithelial vesication and reducing corneal edema using anti‐inflammatory drugs, the effects of SM exposure on other corneal tissues have been largely ignored. Recent studies in vapor‐exposed rabbit eyes have identified several new tissue‐specific pathologies that appear to explicate many aspects of SM injury . Understanding the importance of these pathologies to SM injury progression requires an appreciation of the functional and regenerative capacities of corneal tissues.…”

Section: Tissue‐specific Aspects Of Sm Injury: Overviewmentioning

confidence: 99%

“…An O‐ring is used to restrict SM exposure to the area of the vapor cap, eliminating pericorneal lesions resulting from lateral diffusion. We have used this vapor exposure model to describe dose‐ and time‐dependent effects of SM on the structure, biochemistry, and function of corneal tissues . Briefly, within 24 h of exposure, corneas develop acute lesions characterized by vesication of the corneal epithelium, stromal keratocytosis, corneal edema, and corneal endothelial cell (CEC) loss.…”

Section: Animal Models Of Ocular Sm Injurymentioning

confidence: 99%

Contributions of tissue‐specific pathologies to corneal injuries following exposure to SM vapor

McNutt

Tuznik

Glotfelty

et al. 2016

Annals of the New York Academy of Sciences

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Corneal injuries resulting from ocular exposure to sulfur mustard (SM) vapor are the most prevalent chemical warfare injury. Ocular exposures exhibit three distinct, dose-dependent clinical trajectories: complete injury resolution, immediate transition to a chronic injury, or apparent recovery followed by the subsequent development of persistent ocular manifestations. These latter two trajectories include a constellation of corneal symptoms that are collectively known as mustard gas keratopathy (MGK). The etiology of MGK is not understood. Here, we synthesize recent findings from in vivo rabbit SM vapor studies, suggesting that tissue-specific damage during the acute injury can decrement the regenerative capacities of corneal endothelium and limbal stem cells, thereby predisposing the cornea to the chronic or delayed forms of MGK. This hypothesis not only provides a mechanism to explain the acute and MGK injuries but also identifies novel therapeutic modalities to mitigate or eliminate the acute and long-term consequences of ocular exposure to SM vapor.

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Structural, Morphological, and Functional Correlates of Corneal Endothelial Toxicity Following Corneal Exposure to Sulfur Mustard Vapor

Cited by 35 publications

References 27 publications

Clinical progression of ocular injury following arsenical vesicant lewisite exposure

Clinical progression of ocular injury following arsenical vesicant lewisite exposure

Mustards and Vesicants

Contributions of tissue‐specific pathologies to corneal injuries following exposure to SM vapor

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