Rod and cone function in patients with KCNV2 retinopathy

PLoS One. 2012;7(10):e46762. doi: 10.1371/journal.pone.0046762. Epub 2012 Oct 15.

Abstract

Background: To investigate rod and cone function and disease mechanisms in patients with KCNV2 retinopathy.

Methodology/principal findings: Psychophysical examinations as well as detailed electrophysiological examinations with Ganzfeld and multifocal electroretinogram (ERG) were performed to study response dynamics. Additionally, fundus photography, autofluorescence imaging and spectral domain OCTs were carried out for morphological characterization. Molecular genetic analysis revealed compound heterozygosity in five patients and homozygosity for the KCNV2 gene in one patient. The mutations resulted in complete absence of Kv8.2 subunits in three patients (no protein group, NOP), while the other three patients expressed mutant Kv8.2 subunits resulting in altered Kv2.1/Kv8.2 heteromeric or residual Kv2.1 homomeric potassium channel function (altered protein group, ALP). Although more advanced morphological changes were visible in the NOP group, a clear functional difference between the two groups could not be observed. All patients showed characteristic dynamics of the b-wave intensity-response function, however, scotopic b-wave response amplitudes were within normal limits. We also observed severely reduced oscillatory potentials.

Conclusions/significance: A specific genotype-phenotype correlation in retinal function could not be demonstrated. KCNV2 mutations cause a unique form of retinal disorder illustrating the importance of K(+)-channels for the resting potential, activation and deactivation of photoreceptors, while phototransduction remains unchanged. The reduced oscillatory potentials further suggest an altered function of the inner retina. Besides the characteristically steep amplitude-versus-intensity relationship, flicker responses at intermediate frequencies (5-15 Hz) are significantly reduced and shifted in phase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Female
  • Humans
  • Male
  • Middle Aged
  • Potassium Channels, Voltage-Gated / genetics
  • Potassium Channels, Voltage-Gated / physiology*
  • Psychophysics
  • Retinal Cone Photoreceptor Cells / physiology*
  • Retinal Diseases / physiopathology*
  • Retinal Rod Photoreceptor Cells / physiology*
  • Tomography, Optical Coherence

Substances

  • KCNV2 protein, human
  • Potassium Channels, Voltage-Gated

Grant support

This study was supported in part by the German Research Foundation, Pro Retina Society and the Kerstan & Tistou Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.