Purpose
Megadose steroids are an ineffective and potentially dangerous treatment for TON (Sarkies, Eye 2004;18:1122-5). Development of new treatments has been inhibited by the lack of a suitable animal model of TON. An ideal model would produce symmetric bilateral injury to both nerves without damaging the globe or compromising blood supply. Recent studies indicate that rapid rotation of the globe can produce partial or complete axonal avulsion immediately posterior to the lamina cribrosa (Sponsel et al, IOVS 2011;52:9624-8). Here, we present a robotic torsion device to test whether a rapid rotation could induce optic nerve damage similar to that observed in TON.
Methods
A robot was constructed (Fig. 1) to allow the application of rapid rotation to the eyes of a rat. The magnitude and velocity of rotation were both controlled to allow titration of damage to the optic nerve. The motor’s axis was fastened to the left eye using an elbow clamp holding a suction cup which attached to the eye using an ophthalmodynomometer. Initial testing of the device was carried out by producing torsional trauma to the left eye of a rat cadaver. In half of the animals, the right eye was left uninjured as a control while in the other half an identical injury was inflicted to examine symmetry. Both nerves were examined using biomicroscopy and histopathology.
Results
Controlled rotations up to 120 degrees at velocities of 13500 degrees/second were achieved. Optic nerve damage increased with both the magnitude and rate of rotation. Twisting the eye at a sufficiently high rate and magnitude resulted in a completely severed optic nerve. The control (right) eyes and optic nerves did not exhibit any degree of trauma or other damage induced by application of the device.
Conclusions
The robotic device successfully induced trauma limited to the selected eye, inducing optic nerve damage similar to that observed in human TON patients. The potential to produce isolated, titrated, symmetric injury to the retrolaminar nerve without traumatizing any of the remainder of the visual system using this focalized strain-rate effect offers the ideal model for placebo-controlled bilateral studies of topical, intraocular, or retrobulbar neuroprotective therapies to mitigate the effects of TON. This animal model of torsion-induced TON will next be investigated in live rats by evaluating functional MRI and other measures of visual function.
Keywords: 742 trauma •
629 optic nerve •
637 pathology: experimental