Assessment of the uniform field electroretinogram for mouse retinal ganglion cell functional analysis

Abstract

Purpose : The uniform field electroretinogram (UFERG) has been suggested as an alternative to the pattern electroretinogram (PERG) for the non-invasive assessment of retinal ganglion cell (RGC) function, since both responses appear to originate in similar populations of ganglion cells in primates. We sought to evaluate the validity of the UFERG as a novel tool to assess mouse RGC activity in vivo.

Methods : Optic nerve crush (ONC) was performed on one eye of adult C57BL/6J mice, or not at all, under general anaesthesia. Electrophysiological visual assessment was performed at 12 weeks post-ONC using the Celeris platform (Diagnosys LLC) with integrated stimulator and light guide corneal electrodes. Flash-mediated visual evoked potentials (VEPs) were measured to confirm the robustness of the ONC procedure. Full-field flash ERGs enabled the analysis of photoreceptor, retinal bipolar cell and amacrine cell function by measuring scotopic a-wave, b-wave, and oscillatory potential amplitudes, respectively. RGC function was assessed with a contrast-reversing grating pattern stimulus. UFERG responses to alternating dark and light full-field flash stimuli of different intensities and wavelengths were recorded from ONC and control eyes and relative differences were compared to the PERG results.

Results : ONC did not affect scotopic a-wave and b-wave amplitudes, however it resulted in near complete elimination of VEPs. Uncrushed fellow eyes did not exhibit significant reductions in any functional parameter tested compared to control eyes from mice without surgical manipulation. PERG amplitudes of eyes subjected to ONC were reduced by approximately 50% compared to uncrushed control fellow eyes and eyes from mice without ONC. UFERG responses did not reveal statistically significant differences between ONC and control eyes, regardless of visual stimulus.

Conclusions : ONC is an effective procedure to assess the efficacy of RGC-specific electrophysiological functional tests. PERG responses are dramatically impaired upon ONC, while UFERG responses are not significantly affected by surgical trauma to RGC axons in mice. The related pattern and uniform field ERGs recorded in primates suggests species-specific differences in RGC features or subpopulations corresponding to PERG and UFERG response generators, limiting the utility of the UFERG for mouse RGC functional analysis.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.