Drug Protects Retina after Blast Injury

Palo Alto, CA — Traumatic brain injuries (TBI) can happen when someone is close to an explosion that sends out powerful shock waves through the air. If someone is in the proximity of an exploding munition, like a land mine, they may not have any visible injuries, but internal, life altering injuries may be present. TBI impacts an estimated 2.8 million people worldwide and contributes to over 50,000 deaths per year.

Research has suggested that blast injuries affect vision, and collaborators Vinit Mahajan M.D., Ph.D., professor of ophthalmology at Stanford University, and Alexander Bussuk M.D., Ph.D. at the University of Iowa wanted to know if and how a blast’s shock waves damage the eyes.

Mahajan said, “Because the retina, a thin layer of tissue inside the eye, is made up of similar brain cells, we thought it might be vulnerable to damage from blast-TBI. Our experiments on two different mouse models confirmed that blast-TBI caused damage to the retina, especially the retinal ganglions cells that form the optic nerve.”

“With direct injuries to the eye and retina,” Mahajan added, “we will often perform complex surgeries to restore vision. But indirect blast injuries usually don’t need surgery, since the tissues are intact. There is something more subtle going on.”

In Bussuk’s lab, Medical Student Training Program student Lucy Evans recently identified these subtle changes. She found there were inflammatory molecules in the retina that could damage cells needed for vision.

Evans said, “After the blast, interlekin-1 molecules appeared to be active in the retina, and rheumatologists have targeted these molecules before in humans.”

In research published in the Journal of Neurotrauma, Evans tested whether “repurposing” the already FDA-approved anti-inflammatory drug anakinra would protect the retina after a blast injury. This drug blocks the interleukin-1 receptor. In the mouse model, she found anakinra decreased cellular stress responses and preserved cellular signaling and structure, suggesting that inflammatory blockade in the eye was protective after blast-TBI.

Evans explained, “Our hope is that molecular changes in the eye following blast-TBI may provide valuable information regarding the mechanism, severity, and ongoing pathophysiology of brain injury.”

Dr. Bassuk said, “Since the drug anakinra is already approved by the FDA, it’s possible that swift clinical intervention in blast-TBI patients might preserve vision and brain function and improve their quality of life

Authors of “Modulation of Post-Traumatic Immune Response Using the IL-1 Receptor Antagonist Anakinra for Improved Visual Outcomes” published in Journal of Neurotrauma include:  Lucy P. Evans, Addison W. Woll, Shu Wu, Brittany P. Todd, Nicole Hehr,  Adam Hedberg-Buenz, Michael G. Anderson, Elizabeth A. Newell, Polly J. Ferguson, Vinit B. Mahajan,
Matthew M. Harper and Alexander G. Bassuk