Nawajes Mandal, PhD, professor of Ophthalmology at the University of Tennessee Health Sciences Center, has received a $466,103 grant from the National Eye Institute (NEI) to investigate how blister agents such as mustard gas damage the eye and contribute to long-term vision loss.
The award will support research into the molecular mechanisms underlying ocular injuries caused by chemical warfare agents, with the goal of identifying therapeutic targets that could lead to medical countermeasures, according to a news article posted on the University of Tennessee website. Blister agents—including sulfur mustard, nitrogen mustard, lewisite and phosgene oxime—remain a concern because of their historic use in warfare and their potential for accidental or intentional exposure. Contact with these agents can cause severe injury to the skin, lungs and eyes.
The ocular surface is particularly susceptible to injury following exposure. Acute symptoms can include pain, photophobia and corneal erosions, while long-term complications may include corneal scarring, neovascularization, dry eye disease and permanent vision loss. Currently, no approved therapies specifically prevent or treat blister agent–induced ocular damage.
Dr. Mandal's laboratory will focus on sphingolipids, naturally occurring lipid molecules found in cell membranes that are believed to play a central role in the inflammatory and degenerative processes triggered by blister agent exposure.
Previous preclinical studies conducted by the research team found that nitrogen mustard exposure produced significant corneal inflammation, damage to the cornea and eyelid glands, dry eye-like changes, and profound vision loss in animal models. Analyses from those studies implicated sphingolipid signaling pathways as key drivers of the injury response.
The new funding, awarded through the NIH's R56 mechanism for high-priority research, will enable the group to further investigate the underlying pathobiology and validate the signaling pathways involved.
As part of the project, Dr. Mandal is collaborating with a defense research laboratory at Wake Forest University that has the specialized facilities required to study sulfur mustard, the chemical warfare agent of greatest clinical concern.
"Sulfur mustard is the real threat, not nitrogen mustard," Dr. Mandal said in the UT news article. "We want to correlate whether they produce a similar type of injury at the molecular level."
The researchers aim to determine whether sulfur mustard activates the same lipid signaling pathways identified in nitrogen mustard studies. If confirmed, those pathways could serve as targets for future therapeutic interventions designed to interrupt tissue damage before permanent vision loss occurs.
"Ultimately, the goal is developing medical countermeasures," Dr. Mandal said. "Once we establish the pathway, we are planning to develop some kind of countermeasure to target these lipid pathways."
Looking ahead, Dr. Mandal said the newly funded project is intended to move beyond understanding disease mechanisms toward developing therapies capable of preventing irreversible ocular injury following exposure to chemical blister agents.
"Our objective is not simply to understand the disease," he said. "It is to use that knowledge to develop treatments that preserve vision and improve people's lives."
