In vivo evaluation of optic nerve’s function and structure in large animals by multi-modality analysis

Abstract

Purpose : Large animal models of optic nerve injury are important in translational medicine. We aimed to evaluate and refine the current available evaluation methods for optic nerve function and structure in large animals.

Methods : We employed goats and rhesus macaques in this study. By using goats, we compared the effects of two different anesthesia and different stimulation on flash visual evoked potential (FVEP) and pattern electroretinogram (PERG). We also explored which components in FVEP, PERG, PLR and OCT are more stable and sensitive to optic nerve injury in goat. Finally, we applied the refined FVEP, PVEP, PERG, OCT and PLR to rhesus macaques, and evaluated their reproducibility.

Results : In goats, FVEP recordings with isoflurane were significantly more stable than those with xylazine both in amplitude and latency. FVEP at light intensity of 3.0cd/m² was more variable than those at 0.025 and 0.25cd/m². The intrasession variation of FVEP with the large-Ganzfeld stimulator was significantly smaller than that with mini-Ganzfeld.
PERG waveforms with xylazine were significantly more stable than those with isoflurane both in amplitude and latency. PERG waveform at spatial frequency of 12.6cpd was more variable than those at lower spatial frequencies. Binocular simultaneous stimulation was feasible in goats because there was no interocular crosstalk of PERG signals.
After optic nerve crush, some components of FVEP, like P1 amplitude at 0.025cd/m², P2 amplitude at 0.25cd/m², and P2 latency at 0.025cd/m² changed significantly at most time points post injury compared with the baseline values. In addition, PERG, OCT and PLR data also shown significant changes post injury.
In rhesus macaque, we found that the latencies of early components in PVEP, FVEP and PERG were significantly more stable than amplitudes; and OCT and PLR tests demonstrated low intrasession variation.

Conclusions : In this study, we set up a refined system to evaluate optic nerve’s function and structure in large animals in vivo by multi-modality analysis, which help pave the way for translational research of optic nerve diseases in large animals.

This is a 2020 ARVO Annual Meeting abstract.