Abstract
Purpose :
Traumatic optic neuropathy (TON) is a common cause of vision loss after blunt damage to the ocular orbit. The force is transmitted to the bony optic canal and damages the optic nerve inside the canal. Currently, there is no promising treatment for TON, largely due to the lack of a clinically-relevant, repeatable, quantifiable TON model in large animals with comparable size of optic nerve to human. This study was to develop a TON model relevant to clinical scenario in both goats and rhesus macaques.
Methods :
To recapitulate the clinical scenario, optic canal of the large animas (goats and rhesus macaques) was exposed by the surgical procedure, and then an adjustable force was applied onto the optic canal to damage the intracanalicular optic nerve. Visual function tests (pupillary light reflex (PLR), FVEP, PERG) and retinal OCT were performed to evaluate the severity of optic nerve injury and its progression over 3 months. Retinal ganglion cells (RGCs) were stained with RBPMS. Optic nerve fibers were quantified in semi-thin sections.
Results :
Exposure of optic nerve inside the optic canal could be achieved within 1 hour in goat and 2 hours in macaque under nasal endoscopic surgery. The exposure of intracanalicular optic nerve didn't cause any detectable abnormality in optic nerve's function or structure by the tests mentioned above. After injury, OCT showed progressive reduction of ganglion cell complex thickness. Amplitude of PLR, PERG, FVEP decreased significantly after optic nerve injury. Number of RGCs and optic nerve fiber significantly decreased compared with the base line. Based on this model, we also exposed the optic chiasm, and achieved retrograde staining of RGCs by injecting dyes into the optic chiasm. In addition, we recorded FVEP like signal at the optic chiasm when stimulating the retina with flash light.
Conclusions :
We set up a novel clinically-relevant optic nerve injury model in goats and rhesus macaques by endoscopy in a safe and time-effective way. By using this model, reagents, stem cells and biomaterial could be directly delivered to the local injured optic nerve to modify the micro-environment. This TON large animal model can offer a good opportunity to help bridge the gap between achievements of optic nerve repair in rodents and their clinical application in our TON patients.
This is a 2020 ARVO Annual Meeting abstract.