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Attenuation of oscillatory potentials in nob2 mice

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Abstract

Purpose

To examine changes in inner retinal function of nob2 mice, expressing a null mutation in Cacna1f encoding the CaV1.4 subunit of voltage-dependent calcium channels. 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) b-waves and oscillatory potentials (OPs) are decreased in CSNB2 patients.

Methods

ERGs were recorded under dark-and light-adapted conditions from the corneal surface of nob2 mice, WT littermates and nob4 mice. ERG frequency spectra were calculated by fast Fourier transform (FFT). A FFT-based high-pass filter was used to derive OP waveforms.

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. In response to low stimulus flashes, reliable OPs were not obtained from nob2 mice. OPs were only seen at stimulus intensities at or above −1.8 log cd s/m2, where they occurred at a lower frequency range (70–90 Hz) than for 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 CaV1.4 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 in response to the decreased bipolar cell response in nob2 mice.

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Acknowledgments

This research was supported by the NEI (R01 EY14465; R24 EY15638), the Department of Veterans Affairs, a Challenge grant from Research to Prevent Blindness to the Department of Ophthalmology, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, and a State of Ohio BRTT grant. The authors are grateful to Jiang Wu for care of experimental mice.

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Authors and Affiliations

  1. Cole Eye Institute (I-31), Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH, 44195, USA

    Minzhong Yu & Neal S. Peachey

  2. Cleveland VA Medical Center, Cleveland, OH, USA

    Neal S. Peachey

  3. Department of Ophthalmology, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USA

    Neal S. Peachey

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  1. Minzhong Yu
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  2. Neal S. Peachey
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Correspondence to Minzhong Yu.

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Yu, M., Peachey, N.S. Attenuation of oscillatory potentials in nob2 mice. Doc Ophthalmol 115, 173–186 (2007). https://doi.org/10.1007/s10633-007-9058-9

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  • DOI: https://doi.org/10.1007/s10633-007-9058-9

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