Send to

Choose Destination
Ocul Surf. 2018 Jan;16(1):154-162. doi: 10.1016/j.jtos.2017.11.004. Epub 2017 Nov 10.

Nitrogen mustard-induced corneal injury involves the sphingomyelin-ceramide pathway.

Author information

Department of Environmental Health Sciences, Yale School of Public Health, New Haven, CT, USA.
Gavin Herbert Eye Institute, University of California, Irvine CA, USA.
Department of Clinical Pharmacy, Skaggs School of Pharmacy & Pharmaceutical Sciences, University of Colorado, Aurora, CO, USA.
Department of Environmental Health Sciences, Yale School of Public Health, New Haven, CT, USA; Department of Ophthalmology and Visual Science, Yale School of Public Health, New Haven, CT, USA. Electronic address:



Nitrogen mustard (NM), which simulates the effects of sulfur mustard (SM), is a potent vesicant known to cause irreversible corneal damage. This study investigates the mechanisms by which NM induces corneal damage by examining the impact of NM exposure on the morphology and lipidome of the cornea.


Intact ex vivo rabbit eyes were placed in serum-free DMEM organ culture. NM (0, 1, 2.5, 5 or 10 mg/ml) was applied to the central cornea for 5, 10 or 15 min using a 5 mm filter disk and subsequently rinsed with DMEM. Corneas were then cultured for 3, 24, or 48 h before being fixed for morphological analysis or for 24 h before being snap frozen for lipidomic analysis.


No morphological changes were detected 3 h after NM exposure. Twenty-four h after exposure, 1 mg/ml NM caused erosion of the corneal epithelium, but no damage to the underlying stroma. Damage caused by 2.5 mg/ml NM extended almost two thirds through the corneal stroma, while 5 mg/ml completely penetrated the corneal stroma. An altered lipid profile occurred 24 h after corneas were exposed to NM. Specific sphingomyelins, ceramides, and diacylglycerols were increased up to 9-, 60- and 10-fold, respectively.


NM induces concentration- and exposure time-dependent damage to the cornea that increases in severity over time. Alterations in the sphingomyelin-ceramide pathway may contribute to the damaging effects of NM exposure.


Cornea; Depth of injury; Metabolomics; Nitrogen mustard; Sulfur mustard


Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center