Properties of Rod-Mediated Flicker Assessed in the Cnga3 Mouse Model Lacking Cone Function

Abstract

Abstract: : Purpose: To investigate the properties of flicker electroretinograms (ERGs) in cone cyclic nucleotide-gated channel (Cnga3) knockout mice completely lacking cone function. Methods: Ganzfeld flicker ERGs of different frequencies were obtained in dark-adapted Cnga3 mutant mice using Xenon flash stimuli whose intensities ranged from –4 to 1.4 log (cds/m²) in steps of 0.2 log units. The frequency was varied between 0.75 and 24 Hz. In some cases, additional backgrounds of 0.1, 0.3, and 1.0 cd/m² were applied. A VlogI (Amplitude vs. logarithm of stimulus intensity) function was determined from these data for each combination of parameters. To investigate the nature of the loss of rod flicker amplitude at higher intensities, a series of recordings was performed by keeping the flash intensity constant and adding an equivalent constant background illumination of increasing intensity instead. Results: In general, there was an increase in response amplitude with intensity up to a maximum, followed by a subsequent drop for each frequency tested. Also, the amplitudes obtained at a given intensity were negatively correlated with the frequency (i.e. the amplitudes were lower for high than for low frequencies). The assessment of the cause of the amplitude loss at higher intensities performed at a frequency of 6 Hz suggested that any increase in intensity above the one yielding the peak amplitude (about 10 mcds/m² for the 6 Hz flicker) does not further enlarge the rod response, but instead causes the same decrease as an equivalent constant background. Conclusions: In this study, the properties of flicker electroretinograms in a functionally all-rod mouse were determined. It was found that rods, at an appropriately low stimulus intensity, can follow flicker up to at least 20 Hz like wild-type mice. The loss of amplitude observed for each frequency at higher intensities was identical to the one observed with equivalent backgrounds, indicating that rods ‘see' higher intensity flicker stimuli at least partially as background.

Keywords: electroretinography: non-clinical • retina: distal(photoreceptors, horizontal cell • animal model