TrkB Activators for the Treatment of Traumatic Vision Loss
Technical Report,30 Sep 2014,29 Sep 2015
Emory University Atlanta United States
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Pressure waves due to explosions can damage the neurons of the eye and visual centers in the brain, leading to functional loss of vision. There are currently few treatments for such injuries that can be deployed rapidly in the field to mitigate such damage. Our research team is developing small molecule activators of TrkB, the cognate receptor for brain-derived neurotrophic factor BDNF, which can be administered systemically and cross the blood brainretina barrier BBB. In the third year of the grant, we tested the effects of the TrkB receptor activator, HIOC, in a blast overpressure model of ocular trauma.HIOC produced a significant preservation of visual function, which in some experiments was nearly complete. We also found that HIOC partially prevented optic nerve degeneration following ocular blast injury. HIOC alone was as effective or more effective than combinations of HIOC and meloxicam, an anti-inflammatory drug, or HIOC and FTY720, a drug that converts microglia from an inflammatory phenotype to a neuroprotective phenotype. We also initiated studies to examine the of blast induced head injury. In the initial studies, HIOC partially prevented the loss of visual function caused by blast directed at the head.