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A Practical and Safe Model of Nitrogen Mustard Injury in Cornea
Ana M Sandoval-Castellanos1, Yao Ke2, Tiffany M Dam1
1Department of Ophthalmology & Vision Science, School of Medicine, University of California, Davis, California, 95616, USA.
Biorxiv : the Preprint Server for Biology
|November 1, 2024
Summary
A new mechlorethamine gel model safely replicates sulfur mustard (SM) corneal injuries. This practical approach facilitates research into mechanisms and treatments for devastating SM ocular injuries.
Area of Science:
- Ophthalmology
- Toxicology
- Chemical Warfare Agents
Background:
- Sulfur mustard (SM) causes severe ocular injuries, but its mechanisms remain poorly understood.
- Developing effective treatments is hindered by the lack of safe and practical experimental models.
- The hazardous nature of SM necessitates stringent safety protocols, limiting research accessibility.
Purpose of the Study:
- To establish a novel, safe, and practical laboratory model for studying sulfur mustard-like corneal injuries.
- To utilize mechlorethamine gel, an FDA-approved chemotherapeutic, as a surrogate for SM in corneal injury research.
- To demonstrate the suitability of this model for investigating the histopathological and molecular consequences of mustard-induced ocular damage.
Main Methods:
- Ex vivo porcine corneas were exposed to mechlorethamine gel to induce injury.
- Histopathological analysis included Hematoxylin-eosin staining.
- Immunohistochemistry was employed to assess inflammatory and fibrotic markers, such as cyclooxygenase-2 and fibronectin-1.
Main Results:
- The mechlorethamine gel model successfully induced characteristic histopathological changes, including epithelial damage and stromal separation.
- The model demonstrated consistent expression of inflammation marker cyclooxygenase-2 and fibrosis marker fibronectin-1.
- These findings align with established observations from other sulfur mustard-like corneal injury models.
Conclusions:
- The mechlorethamine gel model provides a safe and accessible method for studying mustard corneal injuries.
- This model facilitates research into the mechanisms underlying ocular damage caused by chemical warfare agents.
- It holds significant potential for accelerating the discovery and development of novel therapeutic interventions for mustard-induced eye injuries.

