Oscillatory Potentials in Achromatopsia as a Tool for Understanding Cone Retinal Functions

Abstract

Achromatopsia (ACHM) is an inherited autosomal recessive disease lacking cone photoreceptors functions. In this study, we characterize the time-frequency representation of the full-field electroretinogram (ffERG) component oscillatory potentials (OPs), to investigate the connections between photoreceptors and the inner retinal network using ACHM as a model. Time-frequency characterization of OPs was extracted from 52 controls and 41 achromat individuals. The stimulation via ffERG was delivered under dark-adaptation (DA, 3.0 and 10.0 cd·s·m−2) to assess mixed rod-cone responses. The ffERG signal was subsequently analyzed using a continuous complex Morlet transform. Time-frequency maps of both DA conditions show the characterization of OPs, disclosing in both groups two distinct time-frequency windows (~70–100 Hz and >100 Hz) within 50 ms. Our main result indicates a significant cluster (p < 0.05) in both conditions of reduced relative power (dB) in ACHM people compared to controls, mainly at the time-frequency window >100 Hz. These results suggest that the strongly reduced but not absent activity of OPs above 100 Hz is mostly driven by cones and only in small part by rods. Thus, the lack of cone modulation of OPs gives important insights into interactions between photoreceptors and the inner retinal network and can be used as a biomarker for monitoring cone connection to the inner retina.

Origin of Retinal Oscillatory Potentials in the Mouse, a Tool to Specifically Locate Retinal Damage

“…Further experiments will need to be performed at the cellular level to address these mechanisms. Finally, we cannot discard the possibility that the reciprocal synapses between OFF-cone bipolar cells and AII Amacrine cells may somehow contribute to OP oscillations, since ERG-OPs recorded from human beings affected by achromatopsia suffer a decrease in the magnitude of the OPs [ 40 ].…”

S-cone contribution to oscillatory potentials in patients with blue cone monochromacy

“…A time–frequency analysis was performed using a complex Morlet wavelet convolution to extract both time and frequency representation of the ERG signal. The formula and the procedures implemented for the time–frequency analysis are the same described in our previous study [ 46 ]. This method allowed to extract different features of the signal, such as frequency (Hz), time (ms) and power (dB, squared of the magnitude).…”

“…Specifically, some researchers highlight the significance of synaptic connections between the rod bipolar axon terminals and amacrine cells [ 44 ], while others propose involvement of ganglion cells [ 43 , 45 ]. In a previous study, we compared OPs between individuals with ACHM and controls, showing that OPs are significantly reduced in the first, but nevertheless present [ 46 ]. These findings emphasize the importance of a functioning cone pathway to the formation of the dark-adapted OPs.…”

Comprehensive variant spectrum of the CNGA3 gene in patients affected by achromatopsia

“…However, in some incomplete achromats reduced photopic responses can be observed (Maguire et al, 2018; Tekavcic Pompe et al, 2021; Zobor et al, 2017). A recent study using time‐frequency analysis of the standard ffERG in ACHM patients compared to age‐matched controls showed a strongly reduced but not absent activity of oscillatory potentials in a frequency range mostly driven by cones and only in a small part by rods (Righetti et al, 2021). This manifestation of the lack of cone modulation on the retinal network gives insights into interactions between both types of photoreceptors and the inner retinal network (Righetti et al, 2021).…”

“…A recent study using time‐frequency analysis of the standard ffERG in ACHM patients compared to age‐matched controls showed a strongly reduced but not absent activity of oscillatory potentials in a frequency range mostly driven by cones and only in a small part by rods (Righetti et al, 2021). This manifestation of the lack of cone modulation on the retinal network gives insights into interactions between both types of photoreceptors and the inner retinal network (Righetti et al, 2021). Similarly, pupillometric measures are objective tests of the retinal function that are able to address cones and rods independently from each other and can reveal reduced cone functionality and preserved or increased rod function due to the missing interaction of cones and rods in the retina of ACHM patients (Kelbsch et al, 2019; Lisowska et al, 2017).…”