Abstract
Purpose :
Retinopathy is increasingly associated with traumatic brain injury. However, the mechanism(s) behind its often insidious pathology are not understood. Although animal models can provide a means to study this complex process, off target injury can complicate the disease picture. Here, we develop a rat model that provides a reproducible system reminiscent of the coup and counter coup/Commotio Retinae pathology.
Methods :
A compressed air driven shock tube delivered 26 psi blast waves from a 3 mm diameter stainless steel nozzle held stereotaxically 2 mm over the cornea of 20 anesthetized age matched adult Sprague-Dawley rats. Body temperature was maintained at 37oC, and heart and breathing rate were monitored. One eye received the blast; sham animals received no blast. After 4 wks under cyclic light: ERGs, electron microscopy, sagittal FFPE sections carefully oriented through the optic nerve and pupil were stained with H&E and PAS. Cell counts of the outer-, inner-nuclear, and ganglion cell layer cell at 400 u intervals were made from digitized scans with QuPath software.
Results :
The animals tolerated the blast without physiological signs of stress, or external evidence of injury to the globe or ocular adnexa. In three animals, hemorrhage over the optic nerve head was noted. Flash intensity plots showed a reduction in ERG a and b wave amplitudes. Cellular morphometrics showed two patterns of degeneration. Pattern 1, Inner Nuclear layer degeneration, or ganglion cell loss with optic nerve degeneration; Pattern 2, Outer Nuclear Layer degeneration with RPE dropout often involving the mid-peripheral retina. EM showed disruption and breaking of rod outer segments, and separation of outer segments from the inner segment compared to controls.
Conclusions :
In vivo focused blast injury to a single eye can be accomplished without external trauma or physiological stress, while also avoiding subjecting the body to the blast wave. Coup injury (posterior retinal hemorrhage and optic nerve trauma), and indirect (countercoup) injury (outer segment disruption and outer-inner segment separation, mid-peripheral outer nuclear layer cell degeneration with RPE loss) were readily produced. The focal single-eye blast model provides a valuable system recapitulating human ocular traumatic injury including Coup and Commotio Retinae, and other countercoup pathology.
This is a 2021 ARVO Annual Meeting abstract.