The Retinal Ganglion Cell Response to Blast-Mediated Traumatic Brain Injury Is Genetic Background Dependent.

Abstract

PurposeThe purpose of this study was to examine the influence of genetic background on the retinal ganglion cell (RGC) response to blast-mediated traumatic brain injury (TBI) in Jackson Diversity Outbred (J:DO), C57BL/6J and BALB/cByJ mice.MethodsMice were subject to one blast injury of 137 kPa. RGC structure was analyzed by optical coherence tomography (OCT), function by the pattern electroretinogram (PERG), and histologically using BRN3A antibody staining.ResultsComparison of the change in each group from baseline for OCT and PERG was performed. There was a significant difference in the J:DOΔOCT compared to C57BL/6J mice (P = 0.004), but not compared to BALB/cByJ (P = 0.21). There was a significant difference in the variance of the ΔOCT in J:DO compared to both C57BL/6J and BALB/cByJ mice. The baseline PERG amplitude was 20.33 ± 9.32 µV, which decreased an average of −4.14 ± 12.46 µV following TBI. Baseline RGC complex + RNFL thickness was 70.92 ± 4.52 µm, which decreased an average of −1.43 ± 2.88 µm following blast exposure. There was not a significant difference in the ΔPERG between J:DO and C57BL/6J (P = 0.13), although the variances of the groups were significantly different. Blast exposure in J:DO mice results in a density change of 558.6 ± 440.5 BRN3A-positive RGCs/mm2 (mean ± SD).ConclusionsThe changes in retinal outcomes had greater variance in outbred mice than what has been reported, and largely replicated herein, for inbred mice. These results demonstrate that the RGC response to blast injury is highly dependent upon genetic background.