A Practical and Safe Model of Nitrogen Mustard Injury in Cornea.

Abstract

Sulfur mustard (SM) is an alkylating agent used in warfare and terrorism that inflicts devastating ocular injuries. Although the clinical symptoms are well described, the underlying mechanisms are not fully understood, hindering the development of effective treatments. One major roadblock is the lack of a suitable model due to the extremely hazardous nature of SM, which requires strict safety measures. As a safe and practical alternative, we report a novel model that uses mechlorethamine (nitrogen mustard) gel, an FDA-approved topical chemotherapeutic administered by patients at home. Here we demonstrate its suitability to induce mustard corneal injury in any laboratory. Ex vivo porcine corneas were injured with mechlorethamine gel. Hematoxylineosin staining, and immunohistochemistry were performed to evaluate histopathology of SM-like corneal injuries: epithelium thickness and stromal separation, keratocyte and inflammatory cell counts, and expression of inflammation and fibrosis markers. This model showed the characteristic histopathology and expression of cyclooxygenase-2 (inflammation) and fibronectin-1 (fibrosis), which were consistent with other well-established SM-like corneal injury models. Given its ease of implementation and safety, this mechlorethamine model could be used to study the full course of mustard corneal injuries. This model would greatly facilitate mustard injury research, shedding light on new knowledge that would increase our understanding of mustard ocular injuries while investigating novel therapeutics. this model will allow safe evaluation of SM-like corneal injuries within 24 hours, facilitating the identification of early/new molecules that might help to develop novel treatments which could be readily translated into the clinic.