Evaluation of Novel Polyunsaturated Fatty Acid Derived Lipid Mediators of Inflammation to Ameliorate the Deleterious Effects of Blast Overpressure on Eye and Brain Visual Processing Centers in Rats

Abstract

Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. 5f. WORK UNIT NUMBER PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT NUMBERThe Geneva Foundation Tacoma, WA 98402 SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR'S ACRONYM(S) U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 SPONSOR/MONITOR'S REPORT NUMBER(S) DISTRIBUTION / AVAILABILITY STATEMENTApproved for Public Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES None ABSTRACTUsing an adult rat model of blast wave exposure, we rigorously characterized the cellular and functional damage to the eyes (retinas) and brain visual processing centers, by electroretinography (ERG), visual discrimination behavioral testing, and histopathology. Blast wave injury was carried out by placing the rats in a compressed air driven shock tube and exposing them, in a right side on orientation, once to a 20 psi (260 Hz) blast over pressure wave. Rats were assessed at baseline and then 1, 7, and 14 days post-exposure. By 7 to 14 days out, blasted rats versus shams showed significantly decreased ERG waveform amplitudes for the right side eyes (~ 30% less; n = 15 vs.14), a trend for impaired ability to visually discern a cue light to earn food rewards (~ 30% less; n = 10 vs. 11), and significant neuronal cell degeneration within the right side retinas and both brain optic tracts (2 and 3-fold more, respectively; n = 11 vs. 11). ERG and histopathology results significantly correlated with each other (r = -0.7). There also was a strong relationship between the retina and brain optic tract cell damage (r = 0.8). Overall, our findings demonstrate that blast wave exposure leads to loss of vision in rats, likely through retinal cell death followed by anterograde degeneration of brain visual processing centers from lack of signaling input.

Vision Recovery and Connectivity by Fetal Retinal Sheet Transplantation in an Immunodeficient Retinal Degenerate Rat Model

“…Electroretinography was performed within 1 month prior to the SC recording (age at testing ranged between 2.5 and 6 months) using the HMsERG system (Ocuscience, Las Vegas, NV, USA) as previously described. 45 , 46 Briefly, rats were dark adapted for a minimum of 2 hours prior to testing. The rats were then anesthetized with ketamine/xylazine and 0.5% to 2% isoflurane.…”