Researchers seek novel inflammatory modulatory protein to treat corneal alkali injury

Temple, TX-Outcomes of an initial pilot study conducted in a preclinical animal model support further research investigating tumor necrosis factor-α stimulated gene/protein-6  (TSG-6) as a novel treatment for chemical injury to the cornea, said Samuel F A Fulcher, MD.

“Current treatments for chemical burns of the cornea are limited and none work particularly well,” said Dr. Fulcher, associate professor of surgery (ophthalmology), Texas A&M Health Science Center, and cornea and external disease specialist, Central Texas Veterans Health Care System, Temple, TX.“Therefore, we are hoping that in this larger animal model, and by modifying different parameters, we may identify potential for TSG-6.”

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TSG-6 is a macrophage-produced protein that has feedback inhibition on the inflammatory response. As a unique characteristic, it acts at the very earliest stage of the inflammatory cascade, which makes it particularly appealing as an intervention for chemical corneal burns or other conditions where tissue damage is modulated by the host inflammatory response incited by the initial injury, Dr. Fulcher said.

After having established that TSG-6 decreased inflammatory damage to the cornea associated with chemical injury and scraping, Dr. Fulcher and colleagues advanced their research into testing the activity of TSG-6 for modulating alkali-induced injury, which is a more common occurrence.

The testing was performed in a mouse model using sodium hydroxide exposure. Animals were treated with TSG-6 either topically (0.1 μg/μl in PBS) or by intravenous (IV) administration (40 μg in 200 μl PBS). Efficacy assessment by measuring myeloperoxidase (MPO) activity as a marker of neutrophil infiltration showed no benefit of topical administration.

IV TSG-6 significantly reduced MPO activity, but had no effect on the development of corneal opacity.

Having received a grant to support further studies, Dr. Fulcher and colleagues are now expanding their investigations to a rat model. They will continue to study both routes of administration with variations in dosing and concentration as well as in the severity of the experimentally induced injury. In addition, they will be measuring additional cytokines as efficacy endpoints and evaluating corneal opacity.