Time-dependent changes in spontaneous and light-evoked retinal ganglion cell activity in a mouse model of blast-induced traumatic brain injury

Abstract

Purpose: To analyse the in vitro function of retinal ganglion cells (RGCs) after exposure to blast.

Methods: Mice were exposed to an overpressure wave (20 PSI) directed to the head using a custom-built blast chamber. Individual RGCs (~ 250 cells for each time point) from freshly dissected whole-mounted retinas were monitored using a multielectrode array at 7 days, 5 weeks and 4 months after exposure to blast. Spontaneous activity and the light evoked responses (to full field flashes) for each RGC were measured and compared with retinas from control mice and across time-points. Statistical analysis was performed using the Mann-Whitney test.

Results: Seven days after blast exposure, the spontaneous activity of RGCs was slightly increased compared to controls. The fraction of cells that responded to the onset of light decreased significantly, while the median response amplitude (spikes/sec) and response duration were similar to those of control RGCs. The median amplitude of responses to light OFF-set increased significantly, while response duration decreased. Five weeks post-blast, spontaneous activity was strikingly increased compared to both controls and 7d recordings. The fraction of cells responding to the onset of light was similar to that at 7d, while median response amplitude and response duration were significantly increased compared to both control and 7d post-blast. OFF response amplitude was significantly increased, while response duration was similar to control levels. By four months post-blast, all these measures of RGC physiology had recovered to near-normal values, similar to those at 7d post-blast.

Conclusions: Exposure to blast induces dramatic alterations in physiological activity of RGCs after an initial period of relatively normal function. These latent effects may indicate an optimal time interval during which such dysfunction may be prevented or ameliorated. The return to more normal RGC function by later time points may reflect the physiology of subpopulations that survive long-term, after a substantial proportion of RGCs die. The differential effects of blast exposure on ON and OFF responses may indicate differential susceptibility of particular RGC types to this injury. Better understanding of the RGC physiology after blast exposure will help in the development of improved clinical testing and treatment of those suffering from TBI.

Keywords: 508 electrophysiology: non-clinical • 531 ganglion cells • 688 retina