ERG and VEP Metrics of Melanopsin Sensitive Ganglion Cells

Abstract

Purpose : Intrinsically photosensitive retinal ganglion cells (ipRGCs) absorb short wavelength light via melanopsin mediating circadian photoentrainment, pupil responses, alertness & cognition, functions which persist despite blindness. Giant ipRGCs, which send signals to LGN/visual cortex implying a role in visual perception, show an inhibitory opponent S cone off response. Human long-latency ipRGC ERGs elicited with silent substitution utilize high contrasts which can lessen ipRGC isolation. We used selective chromatic adaptation to stimulate ipRGCs & S cones to reveal ipRGC ERGs & VEPs (Rabin et al. Eye 2020). Our purpose was to extend this effort & develop new metrics to quantify ipRGCs.

Methods : 20 adults (mean age 25 ± 3, 14 females) participated after informed consent. A Ganzfeld (Diagnosys, LLC) was used to present 200-msec. blue flashes (448 nm) on a rod & LM cone saturating amber background (590 nm, 560 cd/m²) to stimulate S cones (426 nm peak) & ipRGCs (480 nm). Simultaneous flash ERGs and VEPs were recorded in 1000 msec epochs after 30 sec. of adaptation to the amber background over a 4-log unit range (16.7 to .0167 cd/m²). Digital values (µV vs. msec.) were averaged to compute mean ERGs (n=20) & VEPs (n=14). Control ERGs on the amber background showed no ERG to the ISCEV scotopic flash (0.01 cd/m²/sec.) & a small S cone ERG to the 300X brighter standard flash indicating no recordable input from rods, M & L cones.

Results : ERGs revealed a small amplitude S cone ERG followed by a wave of negativity derived from S cone inhibitory input to ipRGCs. Amplitudes were quantified as this negative trough to the first positive peak (ipRGC on response). Log amplitude increased with log luminance (F=13,787, P<.0001, r²=1). ipRGC latency was quantified as the difference between negative trough & positive peak latencies which was highly correlated with amplitude (P<.0001, r²=0.76). The ratio of ipRGC amplitude/latency (throughput) provides a new metric which combines the two variables & is highly dependent on luminance (P<.02, r²=0.76). The flash VEP 1st positive peak (decreased in glaucoma), increased exponentially with ipRGC amplitude (r²=0.91), a potential visual perceptual metric of ipRGCs.

Conclusions : Selective chromatic adaptation reveals retinal & cortical function of ipRGCs, including unique inhibitory input from S cones & putative metrics of visual perception. Planned research will examine pupils using the same visual stimulus.

This is a 2021 ARVO Annual Meeting abstract.