Acute corneal injury in rabbits following nitrogen mustard ocular exposure.
Acute Disease
Animals
Chemical Warfare Agents
/ toxicity
Cornea
/ drug effects
Corneal Injuries
/ chemically induced
Cyclooxygenase 2
/ biosynthesis
Humans
Immunohistochemistry
Interleukin-8
/ biosynthesis
Male
Matrix Metalloproteinase 9
/ biosynthesis
Mechlorethamine
/ toxicity
Mustard Gas
/ toxicity
Rabbits
Vascular Endothelial Growth Factor A
/ biosynthesis
Corneal injury
Inflammation
Mustard
Nitrogen mustard
Sulfur mustard
Vesicant
Journal
Experimental and molecular pathology
ISSN: 1096-0945
Titre abrégé: Exp Mol Pathol
Pays: Netherlands
ID NLM: 0370711
Informations de publication
Date de publication:
10 2019
10 2019
Historique:
received:
23
04
2019
revised:
22
05
2019
accepted:
19
06
2019
pubmed:
25
6
2019
medline:
26
2
2020
entrez:
25
6
2019
Statut:
ppublish
Résumé
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 Metalloproteinase 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.
Identifiants
pubmed: 31233733
pii: S0014-4800(19)30307-7
doi: 10.1016/j.yexmp.2019.104275
pmc: PMC6754274
mid: NIHMS1535004
pii:
doi:
Substances chimiques
Chemical Warfare Agents
0
Interleukin-8
0
Vascular Endothelial Growth Factor A
0
Mechlorethamine
50D9XSG0VR
Cyclooxygenase 2
EC 1.14.99.1
Matrix Metalloproteinase 9
EC 3.4.24.35
Mustard Gas
T8KEC9FH9P
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
104275Subventions
Organisme : NEI NIH HHS
ID : U01 EY023143
Pays : United States
Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.
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