Repetitive mild traumatic brain injury causes optic nerve and retinal damage in a mouse model
There is increasing evidence that long-lasting morphologic and
functional consequences can be present in the human visual system
after repetitive mild traumatic brain injury (r-mTBI). The exact lo-
cation and extent of the damage in this condition are not well un-
derstood. Using a recently developed mouse model of r-mTBI, we
assessed the effects on the retina and optic nerve using histology and
immunohistochemistry, electroretinography (ERG), and spectral-
domain optical coherence tomography (SD-OCT) at 10 and 13 weeks
after injury. Control mice received repetitive anesthesia alone (r-sham).
We observed decreased optic nerve diameters and increased cellularity
and areas of demyelination in optic nerves in r-mTBI versus r-sham
mice. There were concomitant areas of decreased cellularity in the
retinal ganglion cell layer and approximately 67% decrease in brain-
specific homeobox/POU domain protein 3AYpositive retinal ganglion
cells in retinal flat mounts. Furthermore, SD-OCT demonstrated a de-
tectable thinning of the inner retina; ERG demonstrated a decrease in
the amplitude of the photopic negative response without any change in
a- or b-wave amplitude or timing. Thus, the ERG and SD-OCT data
correlated well with changes detected by morphometric, histologic,
and immunohistochemical methods, thereby supporting the use of
these noninvasive methods in the assessment of visual function and
morphology in clinical cases of mTBI.
functional consequences can be present in the human visual system
after repetitive mild traumatic brain injury (r-mTBI). The exact lo-
cation and extent of the damage in this condition are not well un-
derstood. Using a recently developed mouse model of r-mTBI, we
assessed the effects on the retina and optic nerve using histology and
immunohistochemistry, electroretinography (ERG), and spectral-
domain optical coherence tomography (SD-OCT) at 10 and 13 weeks
after injury. Control mice received repetitive anesthesia alone (r-sham).
We observed decreased optic nerve diameters and increased cellularity
and areas of demyelination in optic nerves in r-mTBI versus r-sham
mice. There were concomitant areas of decreased cellularity in the
retinal ganglion cell layer and approximately 67% decrease in brain-
specific homeobox/POU domain protein 3AYpositive retinal ganglion
cells in retinal flat mounts. Furthermore, SD-OCT demonstrated a de-
tectable thinning of the inner retina; ERG demonstrated a decrease in
the amplitude of the photopic negative response without any change in
a- or b-wave amplitude or timing. Thus, the ERG and SD-OCT data
correlated well with changes detected by morphometric, histologic,
and immunohistochemical methods, thereby supporting the use of
these noninvasive methods in the assessment of visual function and
morphology in clinical cases of mTBI.
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