Abstract
Purpose:
The electroretinogram (ERG) a-wave elicited by flashes delivered in the dark largely reflects rod photoreceptor electrical activity. A recent model (Robson & Frishman, Prog Retin Eye Res. 2014; 39:1-22) that takes into account the flow of photo-current in the outer nuclear layer (ONL) in addition to the flow in the sub-retinal space has been shown to fit the kinetics of the response, and, in particular, provides an explanation for the existence and timing of the initial negative peak of the a-wave in responses to strong stimuli. We recorded from normal subjects and from patients with KCNV2 mutations to explore how response kinetics might be altered in KCNV2 retinopathy.
Methods:
Ganzfeld ERG recordings were made from healthy subjects and from 3 patients (from 2 families) with KCNV2 retinopathy, using a conductive fibre electrode following pharmacological pupil dilatation. Responses to white xenon flashes (0.65 to 260 photopic cd s m-2) were recorded in the dark and subsequently in the presence of a blue rod-saturating background (30 scotopic cd m-2). Subtraction of the latter responses from the former yielded isolated rod-driven a-waves.
Results:
Responses to the stronger stimuli in healthy subjects were well fit by the model up until after the negative peak of the a-wave. In the KCNV2 patients, the characteristic early peak and initial recovery of the a-wave towards the baseline was absent or diminished. This is consistent with a reduction in the contribution from the ONL, possibly due to reduced resistivity of this layer. A reduction in the diameter (or number) of rod axons in this layer could give this effect; applying the same model, with an assumed halving of axon diameter gave a reasonable fit to the patients’ a-wave responses.
Conclusions:
The delayed onset of the b-wave in KCNV2 patients has previously been taken to indicate altered inner retinal function. However, accepting that early a-wave peak can be attributed to transient photocurrents within the ONL, the loss of the early peak in KCNV2 patients indicates an altered current flow in the ONL. This is consistent with the localisation of KCNV2 expression to the photoreceptors rather than the inner retina. Our findings suggest that KCNV2 retinopathy could be explained by a reduction in the ONL resistivity, possibly due to a reduction in the diameter or number of rod axons.