The spatial-temporal reactive changes of compressed optic nerve in a clinically relevant rabbit model of persistent compressive optic nerve axonopathy.

The optic nerve (ON) can get compressed in different diseases. However, the pathological and functional changes occurring in the compressed ON over time under constant compression are still unclear. In the present study, we implanted an artificial tube around the optic nerve of a rabbit to primarily create a clinically relevant persistent compressive optic nerve axonopathy (PCOA). Due to the protuberance on the inner ring of the tube, steady and persistent compressions were maintained. In this model, we investigated the thickness of ganglion cell complex (GCC), retinal ganglion cell (RGC) density, axon density of optic nerve, flash visual evoked potential (FVEP), and anterograde axonal transport at various times in four different groups viz. the no comp, 1/2 comp, 3/4 comp, and crush groups. The GCC thickness, RGC density, and axon density of ON were hierarchically and significantly decreased in 1/2 comp, 3/4 comp, and crush groups. Compared to no comp eyes, the P2 amplitude ratio of FVEP was significantly decreased in 3/4 comp but not in 1/2 comp eyes. Only a portion of the optic nerve lost the ability of anterograde axonal transport in the 1/2 comp group. However, it was evident at 2-wpo and more prominent at 4-wpo in 3/4 comp eyes. This study reveals that the compression only induces the homolateral ON axons impairment and the proportion of the affected axons maintains the same for mild compression for at least three months. Furthermore, an underlying threshold effect highlights that mild compression does not require urgent surgery, while the severe compression warrants immediate surgical intervention.

Optic chiasmatic potential by endoscopically implanted skull base microinvasive biosensor: a brain-machine interface approach for anterior visual pathway assessment.

Background: Visually evoked potential (VEP) is widely used to detect optic neuropathy in basic research and clinical practice. Traditionally, VEP is recorded non-invasively from the surface of the skull over the visual cortex. However, its trace amplitude is highly variable, largely due to intracranial modulation and artifacts. Therefore, a safe test with a strong and stable signal is highly desirable to assess optic nerve function, particularly in neurosurgical settings and animal experiments. Methods: Minimally invasive trans-sphenoidal endoscopic recording of optic chiasmatic potential (OCP) was carried out with a titanium screw implanted onto the sphenoid bone beneath the optic chiasm in the goat, whose sphenoidal anatomy is more human-like than non-human primates. Results: The implantation procedure was swift (within 30 min) and did not cause any detectable abnormality in fetching/moving behaviors, skull CT scans and ophthalmic tests after surgery. Compared with traditional VEP, the amplitude of OCP was 5-10 times stronger, more sensitive to weak light stimulus and its subtle changes, and was more repeatable, even under extremely low general anesthesia. Moreover, the OCP signal relied on ipsilateral light stimulation, and was abolished immediately after complete optic nerve (ON) transection. Through proof-of-concept experiments, we demonstrated several potential applications of the OCP device: (1) real-time detector of ON function, (2) detector of region-biased retinal sensitivity, and (3) therapeutic electrical stimulator for the optic nerve with low and thus safe excitation threshold. Conclusions: OCP developed in this study will be valuable for both vision research and clinical practice. This study also provides a safe endoscopic approach to implant skull base brain-machine interface, and a feasible in vivo testbed (goat) for evaluating safety and efficacy of skull base brain-machine interface.