Modelling the rod-driven electroretinogram a-wave elicited by strong flashes: insights from patients with selected post-phototransduction impairments

Abstract

Purpose : The electroretinogram (ERG) elicited by bright flashes in the dark contains rod, cone and post-receptoral contributions. The initial recovery following the a-wave trough has been attributed to intrusion of depolarising ON bipolar cell currents. Robson & Frishman (Prog Retin Eye Res. 2014) described a model (RF model) whereby the trough and initial recovery arises instead from current flows within the outer nuclear layer (ONL). We applied the model to extracted rod-driven a-waves in healthy individuals and in patients with selected rare post-phototransduction impairments.

Methods : ERGs were recorded (conductive fibre electrodes, after pupil dilation) to strong white flashes (50 cd m^-2 s or stronger) in the dark and on a dim blue rod-saturating background (1.3 photopic and 30 scotopic cd m^-2). Subtraction of the latter (cone-driven) responses from the former (rod and cone-driven) yielded the estimated rod-driven response. The RF model was applied.

Results : ERGs were analysed from >100 healthy adults and from patients with the following disorders: central retinal artery occlusion (CRAO; n=1); congenital stationary night blindness (CSNB) associated with variants in NYX, TRPM1, CACNA1F, CABP4 (n=1 for each); KCNV2-retinopathy (n=6). In control individuals, the estimated rod-driven ERG showed a sharp a-wave trough and rapid initial recovery; the model provided a reasonable fit to the a-wave including the initial recovery. The trough and initial recovery were clearly present in recordings from the CRAO and CSNB patients. The model again provided a reasonable fit over a similar region, though still undershooting at later times. In patients with KCNV2-retinopathy, the a-wave seemed to plateau with the model fitting only with substantial reduction in contributions from ONL current flows.

Conclusions : Given that the CRAO and CSNB cases had absent or attenuated ON bipolar signals (either exclusively or in addition to loss of OFF bipolar signals), our findings are consistent with the initial a-wave recovery arising from photoreceptor current flows. This component was lost in KCNV2-retinopathy. The changed contributions could arise from altered channel conductance or reductions in rod photoreceptor axon numbers or diameters. This would be consistent with the ONL thinning that has been reported in these patients.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.