Abstract
Purpose :
The function of intrinsically photosensitive retinal ganglion cells (ipRGCs) after repeated traumatic brain injury (rTBI) is uncharacterized. The purpose of this study was to test the hypothesis that rTBI alters the light adaptation of murine ipRGCs.
Methods :
Adult wild-type C57BL/6 mice were split into two cohorts. The case cohort (n = 48) received one closed-skull strike (1 mm impact depth using a 5 mm tip moving at 5 m/s) from a controlled cortical impactor every 48 hr for 10 d. The control cohort (n = 41) received only anesthesia on the same schedule. Mice from both cohorts were sacrificed 1 mo, 2 mo, or 3 mo after rTBI or anesthesia. In vitro multielectrode array recordings were made from their dissected retinas in response to four exposures of bright (1015 phot/s/cm2) blue (470 nm) light, flickering (0.1 Hz) for 30 seconds (3 pulses of 5 s light). NBQX and L-AP4 isolated the intrinsic ipRGC photoresponses during the fourth exposure. ipRGC action potential spikes from the third and fourth light exposures were counted in 1 s bins and were separated into responses to the first, second, and third pulses. For each cell, spikes in response to the second and third pulses were normalized to spikes during the first pulse. A linear regression model then was fit to the normalized responses to quantify the pulse-by-pulse rate of light adaptation. T-tests compared the rate of adaptation between the two cohorts at each sacrifice time point (α = 0.05).
Results :
Under synaptic blockade, there was no significant difference between the cohorts in the rate of light adaptation (mean [SEM]) at the 1 mo (case -0.13 [0.02], control -0.17 [0.05]), 2 mo (case -0.14 [0.04], control -0.02 [0.07]), and 3 mo (case -0.04 [0.02], control -0.06 [0.04]) time points. Without blockers, there were no significant differences in the rate of light adaptation between the cohorts at the 1 mo (cases -0.17 [0.02], controls -0.18 [0.03]) and 3 mo (case -0.13 [0.02], control -0.12 [0.02]) time points. Adaption was significantly more rapid (p = 0.01) in the cases (-0.16 [0.01]) than in the controls (-0.05 [0.05]) at the 2 mo time point.
Conclusions :
Case ipRGCs showed more light adaptation (i.e., less spiking during each subsequent pulse) than control ipRGCs at 2 mo under normal conditions. This finding is consistent with previous works that reported reduced in vivo RGC function after rTBI and may support a role for ipRGCs in TBI pathology.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.