Elucidation of Inflammation Processes Exacerbating Neuronal Cell Damage to the Retina and Brain Visual Centers as Quest for Therapeutic Drug Targets in Rat Model of Blast Overpressure Wave Exposure
Technical Report,30 Sep 2014,29 Sep 2017
The Geneva Foundation Tacoma United States
Pagination or Media Count:
A frequent cause of traumatic eye injuries to soldiers is exposure to blast shock waves and it can involve cellular damage to the retina as well as brain visual centers. Since there are relatively few animal studies that have studied this, there is an urgent need to advance the characterization of blast induced visual system injuries and identify potential drug therapies. Inflammation plays a key role in the destruction of injured neuronal tissues, as carried out by immune cells and thus is a promising target. Scope and timing, however, of this process must be better understood. Our study uses an adult rat model of eye and brain injuries, as produced by exposure to simulated blast waves in a shock tube. Rats were kept on an omega-3 polyunsaturated fatty acid deficient diet, which promotes inflammation. Conversely, some are fed an omega-3 enriched diet by ocean fish oil supplementation. Up to one month after blast, eye retina and brain damage was assessed by electroretinography ERG, visual acuity task, magnetic resonance imaging MRI, histopathology, and immunoassay arrays for inflammation signaling factors. Our findings revealed that blast exposure leads to long lasting impairments of visual function i.e., out to 28 days with an acute underlying infiltration of activated immune cells e.g. macrophages in the retina and brain i.e., by 3 days, which is accompanied by elevated cytokines and degeneration of neurons. Recovery of retinal function is very gradual with reoccurring signs of neuroinflammation. Despite having potent anti-inflammatory properties, continuous high doses of dietary omega-3 showed only a modest ability to alleviate these injury events, which was most apparent at the chronic phase. Thus, omega-3 supplementation is a supportive rather than first line treatment approach. Overall, our mission is to provide results that will lead to new therapeutic countermeasures for blast-induced damage sustained to the visual system of US Army personnel.
- Medicine and Medical Research
- Anatomy and Physiology