A new and reliable animal model for optic nerve injury.
OBJECTIVE
To create an animal (rat) model of force percussion injury (FPI) to the optic nerve for clinical and experimental research.


METHODS
Seventy-one healthy female Wister rats, with no ocular disorders, were used in this study. Sixty-six rats were subjected to bilateral blunt trauma to the eyes via FPI; five rats were not subjected to trauma. According to the degree of optic nerve injury, injured eyes were divided into two groups: severe optic nerve injury group, with beat pressures of 699.14 ± 60.79 kPa and mild optic nerve injury group, with beat pressures of 243.18 ± 20.26 kPa. Eight rats were examined using flash visual-evoked potential (F-VEP) monitoring and magnetic resonance imaging (MRI) before, 1 and 3 days, and 1, 2, 4, 6, and 8 weeks after optic nerve injury. Fifty-six rats were examined by histopathology and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay for apoptosis at 1 and 3 days, and 1, 2, 4, 6, and 8 weeks after optic nerve injury. Two rats were examined by transmission electron microscopy (TEM) 4 and 8 weeks after optic nerve injury. The presence or absence of optic nerve injury was evaluated in all trauma eyes.


RESULTS
Latency was prolonged in the severe injury group compared with controls 1 day after optic nerve injury (p < .05). Amplitude decreased during the first 2 weeks after optic nerve injury (p < .05) and then stabilized (p > .05). Latency was prolonged in the mild optic nerve injury group compared with controls 1 day after optic nerve injury (p < .05) Amplitude decreased during the first 4 weeks (p < .05) following injury and then stabilized (p > .05). As measured by MRI, an abnormally high signal was seen 1 day after injury and remained significantly high 8 weeks after injury. A ruptured capillary was detected in the ganglion cell layer (GCL) 1 day after injury. Acellular regions in the ganglion cell layer were observed 4 weeks after optic nerve injury. TUNEL-positive cells were present in each layer of the retina 3 days after injury. The number of TUNEL-positive cells began to increase 1-2 weeks after injury, and then gradually decreased 4 weeks after injury (p < .05).


CONCLUSIONS
We successfully created a reproducible experimental animal (rat) model of optic nerve injury using FPI. Optic nerve injury was demonstrated by F-VEP and MRI, and confirmed histologically. Our model is a simple, reliable, reproducible, and stable tool for use in investigations on the mechanism(s) of and treatment for optic nerve injury.
Department of Ophthalmology, Tianjin Medical University General Hospital, Tianjin, China. phuayan2000@yahoo.com
Hua
H
Yan
Fengling
F
Li
Linlin
L
Zhang
D000818:Animals; D001308:Auditory Perceptual Disorders; D001369:Axons / Q000473:pathology / Q000648:ultrastructure; D004195:Disease Models, Animal; D005260:Female; D008279:Magnetic Resonance Imaging; D046529:Microscopy, Electron, Transmission; D009186:Myelin Sheath / Q000473:pathology / Q000648:ultrastructure; D009900:Optic Nerve / Q000473:pathology / Q000648:ultrastructure; D020221:Optic Nerve Injuries / Q000473:pathology* / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D012165:Retinal Ganglion Cells / Q000473:pathology / Q000648:ultrastructure; D015599:Trauma Severity Indices; D014949:Wounds, Nonpenetrating / Q000473:pathology / Q000503:physiopathology