US Department of Defense
Advancing Blast Injury Research to Protect and Heal Those Who Serve

Pathogenesis of blast-induced optic neuropathy

The optic nerve carries information from the retina to the brain. Trauma to, and degeneration of, the optic nerve causes a chronic condition characterized by severe vision loss, known as traumatic optic neuropathy (TON). Neither penetrating damage nor blunt trauma are required to induce TON; indeed, exposure to blast overpressure is sufficient for causing TON.1

In a new study, Dr. Tonia Rex and her Vanderbilt University colleagues endeavored to study primary blast-induced TON to better understand its mechanism(s) and to develop effective treatment strategies.2

Anesthetized mice were placed in a padded pipe with only their left eyes exposed to the barrel of an unloaded paintball marker. This design induces primary blast injury without concurrent head or body damage. A group of mice experienced repeated blasts, while a sham group experienced only the sound of the blast. Comparisons between groups included intraocular pressure (IOP), retinal ganglion cell (RGC) loss, optic nerve degeneration, preservation of visual field representation in the brain, and optic nerve morphology. Observations were made up to 30 days after blast exposure.

Blast-exposed eyes exhibit marked changes indicating damage. IOP increases significantly – though transiently – and the ganglion cell layer of the retina sustains reductions in cell count. The optic nerve loses axons along its entire length from the eye to the brain, with signs of degeneration peaking 14 days after the blast. Furthermore, glial area and select inflammatory markers in the optic nerve increase after blast-induced TON.

The group looked at how this degeneration might affect vision. Specifically, the team can probe how the retina is able to communicate with a region of the mouse's midbrain, the superior colliculus, which functions as a kind of neural representation of the mouse's visual field, or a "retinotopic map." They use a special tracer that moves along the direction of the signal from the retina; when injected into the eye, they reveal how degeneration of the optic nerve impairs vision by determining which portions of the retinotopic map are disturbed. After blast-induced TON, more and more of the retina, starting at the periphery and moving toward the center, loses its representation in the superior colliculus.

Rex and coworkers are the first to describe the pathogenesis of blast-induced TON after the acute phase of trauma. Changes to the optic nerve after blast exposure are distinct from those observed in chronic optic neuropathy, such as glaucoma, in which degeneration starts at one end of the optic nerve and progresses to the other. Importantly, this study suggests that the optic nerve degenerates in two phases after blast exposure; a rapid early phase, presumably in direct response to the blast, and a slower second phase due to increases in oxidative stress and inflammation that follow the blast.3

The study may ultimately lead to new diagnostics and treatments for Soldiers suffering from vision loss. The choice to study mice after repeated exposures to air blasts was made in part for its relevance to Warfighters who can experience multiple blast exposures in theatre from improved explosive devices or artillery fire. The discovery that blast-induced TON is a discrete phenomenon with its own unique pathology, demands follow-up investigation to develop new therapeutic approaches for wounded Warriors.


1 Sarkies, N. (2004). "Traumatic optic Neuropathy." Eye 18, 1122-1125.

2 Bernardo-Colón A, Vest V, Cooper ML, Naguib SA, Calkins DJ, and Rex TS (2019). "Progression and Pathology of Traumatic Optic Neuropathy from Repeated Primary Blast Exposure." Frontiers in Neuroscience 13:719.

3 Bernardo-Colón A, Vest V, Clark A, Cooper ML, Calkins DJ, Harrison FE, and Rex TS (2018). "Antioxidants Prevent Inflammation and Preserve the Optic Projection and Visual Function in Experimental Neurotrauma." Cell Death & Disease, 9(11), 1097.

Last modified: 03-Sep-2019