Abstract
Purpose::
To examine changes in inner retinal function under dark-adapted and light-adapted condition in nob2 mice, expressing a null mutation in Cacna1f encoding CaV4.1. CACNA1F mutations underlie one form of incomplete X-linked congenital stationary night blindness (CSNB2). In addition to a loss of dark-adapted (rod-driven) visual sensitivity, electroretinogram (ERG) components generated by the inner retina (b-wave from bipolar cells; oscillatory potentials (OPs) from amacrine cells) are decreased in CSNB2 patients, although the function of rod photoreceptors appears to be normal.
Methods::
ERGs were recorded under dark- and light-adapted conditions from the corneal surface of anesthetized (ketamine/xylazine) nob2 mice and WT littermates. ERG frequency spectra were calculated by fast Fourier transform (FFT). OP waveforms were derived by a FFT-based high pass filter.
Results::
Under dark-adapted conditions, the dominant frequency of the OPs varied between 90 to 120 Hz in WT mice. In WT mice, OP frequency first increased with flash intensity and then decreased at the highest flash levels while overall OP amplitude increased monotonically with increasing flash intensity. Under low stimulus conditions, reliable OPs were not obtained from nob2 mice. Only at the higher stimulus intensities (≥ -1.8 log cd s/m2), were OPs seen in nob2 animals, at a lower frequency range (70 to 90 Hz) than seen in WT mice. When flash stimuli were superimposed against a steady rod-desensitizing adapting field, the amplitude and frequency of WT OPs increased with flash intensity above 0.4 log cd s/m2. In comparison to WT results, cone-mediated OPs obtained from nob2 mice were smaller in amplitude, of lower frequency and had delayed implicit times. We compared the extent to which OPs and the b-wave were reduced in nob2 mice, by normalizing to the results obtained from WT mice. In comparison to the b-wave, the OPs were relatively spared, under both dark- and light-adapted conditions.
Conclusions::
In nob2 mice, rod- and cone-driven OPs are reduced in amplitude and occur at a lower frequency range. Since CaV4.1 is expressed in both the inner and outer plexiform layers, these changes are likely to reflect reduced transmission from photoreceptors to bipolar cells as well as alterations in inner retinal function. That the OPs were better preserved than b-waves suggests that inner retinal pathways may be reorganized secondary to reduced bipolar cell activity in nob2 mice.
Keywords: electroretinography: non-clinical • gene/expression • retina