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Published on: April 7, 2014
Corneal toxicity induced by vesicating agents and effective treatment options
Dinesh G Goswami1, Neera Tewari-Singh1, Rajesh Agarwal1
1Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
Abstract:
The vesicating agents sulfur mustard (SM) and lewisite (LEW) are potent chemical warfare agents that primarily cause damage to the ocular, skin, and respiratory systems. However, ocular tissue is the most sensitive organ, and vesicant exposure results in a biphasic injury response, including photophobia, corneal lesions, corneal edema, ulceration, and neovascularization, and may cause loss of vision. There are several reports on ocular injury from exposure to SM, which has been frequently used in warfare. However, there are very few reports on ocular injury by LEW, which indicate that injury symptoms appear instantly after exposure and faster than SM. In spite of extensive research efforts, effective therapies for vesicant-induced ocular injuries, mainly to the most affected corneal tissue, are not available. Hence, we have established primary human corneal epithelial cells and rabbit corneal organ culture models with the SM analog nitrogen mustard, which have helped to test the efficacy of potential therapeutic agents. These agents will then be further evaluated against in vivo SM- and LEW-induced corneal injury models, which will assist in the development of potential broad-spectrum therapies against vesicant-induced ocular injuries.
Insights
Sulfur mustard and lewisite cause severe eye injuries. New models using nitrogen mustard help test therapies for these chemical warfare agent-induced corneal damage.
Area of Science:
- Ophthalmology
- Toxicology
- Chemical Warfare Agents
Background:
- Sulfur mustard (SM) and lewisite (LEW) are chemical warfare agents causing significant ocular damage.
- Ocular tissue is highly sensitive to vesicants, leading to conditions like photophobia, corneal lesions, and potential vision loss.
- Limited research exists on lewisite-induced ocular injuries, and effective therapies for vesicant-induced corneal damage are lacking.
Purpose of the Study:
- To establish in vitro and ex vivo models for evaluating therapeutic agents against vesicant-induced ocular injuries.
- To investigate potential broad-spectrum therapies for corneal damage caused by chemical warfare agents.
Main Methods:
- Established primary human corneal epithelial cells and rabbit corneal organ culture models.
- Utilized nitrogen mustard, an analog of sulfur mustard, to simulate vesicant exposure in these models.
- Proposed further evaluation of therapeutic agents in vivo using SM- and LEW-induced corneal injury models.
Main Results:
- Developed functional in vitro and ex vivo models for testing therapeutic efficacy against corneal injury.
- These models facilitate the screening of potential treatments for vesicant-induced ocular damage.
Conclusions:
- The established models provide a platform for developing effective therapies against ocular injuries caused by chemical warfare agents like sulfur mustard and lewisite.
- This research aims to advance the development of broad-spectrum treatments for severe corneal damage.
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