Changes in Retinal Function and Glial Reaction in an Impact Concussion Mouse Model

Abstract

Purpose : A large proportion of enlisted men and women suffer traumatic brain injuries (TBIs) in accidents during training and deployment, in combat, and in “domestic” incidents. Since the retina is the most accessible part of the brain, the eye may serve as a literal window into TBI. Neuroinflammation and glial reaction have been observed in the brains of veterans (and athletes) with chronic traumatic encephalopathy consequent to TBI (see Goldstein et al.). Trauma-induced changes in the retina may both be concomitant to brain dysfunction and contribute to visual dysfunction. Therefore, we evaluated retinal changes in an impact concussion mouse model.

Methods : We examined 27 mice expressing green fluorescent protein in microglia one day before and three days after concussive head injury (HI, n=14) or sham (CT, n=13) treatment. We performed electroretinographic (ERG) testing in all mice (14 HI, 13 CT) and adaptive optics (AO) retinal imaging in a subset (5 HI, 4 CT). We recorded ERG responses to a >5 log unit range of full-field stimuli and obtained measures of the sensitivity and saturated amplitude of photoreceptor (a-wave), postreceptor (b-wave) and inner retinal (OPs) activity. We expressed all values as the log change from baseline (ΔLogNormal) prior to statistical evaluation. We then used a semi-automated approach to label microglia in AO fluorescent scanning light ophthalmographs (AO-fSLOs) of a region near the optic nerve head (ONH).

Results : Following impact, we found modest but significant attenuation in photoreceptor (-0.12 log; -23%), postreceptor (-0.07 log; -15%), and inner retinal (-0.16 log; -31%) responses which did not occur in CT mice. We could readily resolve microglia and their ramifications in AO-fSLO images and, at the second test, found a marked increase in the number of microglia near the ONH in HI mice. Further, microglia were regularly distrubuted and in resting morphology at baseline but, after injury in HI mice, we observed marked microgliosis characterized by reactive phenotype with extensively overlapping ramifications and apparent perivascular reactivity.

Conclusions : Decrease in function, and corresponding glial reaction, occur in retinae following concussive injury. These retinal changes may be of prognostic value in TBI and may underpin some of the vision complaints of veterans with a history of TBI.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.