Abstract
Purpose :
Circadian rhythm abnormalities are reported in patients follwing concussion and moderate brain trauma early in the injury timeline. These include abnormal timing and duration of the sleep cycle, reduction of melatonin levels during the night, and alternating expression of clock genes. Although these deficits could be caused by dysregulation within several brain sites, the retina has been postulated as one of the earliest neural structures affected in serveral neurodegenerative conditions. Melanopsin-expressing retinal ganglion cells (mRGCs) are responsible for maintaining circadian rhythms, thus making the retina an attractive target for investigating pathological mechanisms. Loss and or changes in morphology of mRGCs has been reported in other neurodegenerations such as Parkinson’s disease and glaucoma, however, little is known about the progression of pathology in mRGC axons following traumatic brain injury (TBI).
Methods :
Using a combination of immunohistochemistry and high-resolution fluorescent microscopy, we examined mRGC morphology and corresponding brain projections at two post injury timepoints following a non-repetitive, open skull controlled cortical impact (CCI) in C57/Bl6 mice. Neurolucida 360 software was used to recontruct mRGC profiles in the retina and to determine dedritic field area, number of branch points, and cable length. Neuroinflammatoryand synaptic markers were used to determine integrity of projection sites.
Results :
Our results indicate significant reduction in dendritic field complexity and area, despite an unaltered cell density in the retina of injured subjects 1-week after injury. These results suggest mRGC morphology is altered as a result of injury, which may impact their function. This could help explain non-image forming sequelae following brain trauma.
Conclusions :
In conclusion, early changes in mRGC morphology may contribute to the irregular sleep patterns observed in TBI patients. The accessibility, isolation, and simplicity of the anterior visual system may provide a useful framework for studying the mechanisms of axonopathy following brain injury.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.