Acute corneal injury in rabbits following nitrogen mustard ocular exposure.

Published on Jun 21, 2019in Experimental and Molecular Pathology2.28
· DOI :10.1016/J.YEXMP.2019.104275
Dinesh G Goswami8
Estimated H-index: 8
(Anschutz Medical Campus),
Rama Kant8
Estimated H-index: 8
(Anschutz Medical Campus)
+ 5 AuthorsRajesh Agarwal104
Estimated H-index: 104
(Anschutz Medical Campus)
Sources
Abstract
Abstract Sulfur mustard (SM), a potent vesicating chemical warfare agent, and its analog nitrogen mustard (NM), are both strong bi-functional alkylating agents. Eyes, skin, and the respiratory system are the main targets of SM and NM exposure; however, ocular tissue is most sensitive, resulting in severe ocular injury. The mechanism of ocular injury from vesicating agents' exposure is not completely understood. To understand the injury mechanism from exposure to vesicating agents, NM has been previously employed in our toxicity studies on primary human corneal epithelial cells and ex vivo rabbit cornea organ culture model. In the current study, corneal toxicity from NM ocular exposure (1%) was analyzed for up to 28 days post-exposure in New Zealand White male rabbits to develop an acute corneal injury model. NM exposure led to conjunctival and eyelid swelling within a few hours after exposure, in addition to significant corneal opacity and ulceration. An increase in total corneal thickness and epithelial degradation was observed starting at day 3 post-NM exposure, which was maximal at day 14 post-exposure and did not resolve until 28 days post-exposure. There was an NM-induced increase in the number of blood vessels and inflammatory cells, and a decrease in keratocytes in the corneal stroma. NM exposure resulted in increased expression levels of cyclooxygenase-2, Interleukin-8, vascular endothelial growth factor and Matrix Metallopeptidase 9 indicating their involvement in NM-induced corneal injury. These clinical, biological, and molecular markers could be useful for the evaluation of acute corneal injury and to screen for therapies against NM- and SM-induced ocular injury.
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Abstract Purpose The sight threatening sulfur mustard (SM) induced ocular injury presents specific symptoms for each clinical stage. The acute injury develops in all of the exposed eyes and is characterized by erosions and severe inflammation. The irreversible late pathology develops only in part of the eyes, and is clinically expressed by chronic inflammation and corneal neovascularization (NV). The mechanisms underlying this injury are still in research and treatment is insufficient. Aiming to...
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