Electrical stimulation of inner retinal neurons in wild-type and retinally degenerate (rd/rd) mice

PLoS One. 2013 Jul 11;8(7):e68882. doi: 10.1371/journal.pone.0068882. Print 2013.

Abstract

Electrical stimulation of the retina following photoreceptor degeneration in diseases such as retinitis pigmentosa and age-related macular degeneration has become a promising therapeutic strategy for the restoration of vision. Many retinal neurons remain functional following photoreceptor degeneration; however, the responses of the different classes of cells to electrical stimuli have not been fully investigated. Using whole-cell patch clamp electrophysiology in retinal slices we investigated the response to electrical stimulation of cells of the inner nuclear layer (INL), pre-synaptic to retinal ganglion cells, in wild-type and retinally degenerate (rd/rd) mice. The responses of these cells to electrical stimulation were extremely varied, with both extrinsic and intrinsic evoked responses observed. Further examination of the intrinsically evoked responses revealed direct activation of both voltage-gated Na(+) channels and K(+) channels. The expression of these channels, which is particularly varied between INL cells, and the stimulus intensity, appears to dictate the polarity of the eventual response. Retinally degenerate animals showed similar responses to electrical stimulation of the retina to those of the wild-type, but the relative representation of each response type differed. The most striking difference between genotypes was the existence of a large amplitude oscillation in the majority of INL cells in rd/rd mice (as previously reported) that impacted on the signal to noise ratio following electrical stimulation. This confounding oscillation may significantly reduce the efficacy of electrical stimulation of the degenerate retina, and a greater understanding of its origin will potentially enable it to be dampened or eliminated.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Electric Stimulation / methods
  • Genotype
  • Membrane Potentials / genetics
  • Membrane Potentials / physiology
  • Mice
  • Mice, Inbred C57BL
  • Potassium Channels, Voltage-Gated / genetics
  • Potassium Channels, Voltage-Gated / metabolism
  • Presynaptic Terminals / metabolism
  • Presynaptic Terminals / physiology
  • Retina / metabolism
  • Retina / physiology*
  • Retina / physiopathology
  • Retinal Degeneration / genetics
  • Retinal Degeneration / metabolism
  • Retinal Degeneration / physiopathology*
  • Retinal Ganglion Cells / metabolism
  • Retinal Ganglion Cells / physiology*
  • Vision, Ocular / genetics
  • Vision, Ocular / physiology
  • Voltage-Gated Sodium Channels / genetics
  • Voltage-Gated Sodium Channels / metabolism

Substances

  • Potassium Channels, Voltage-Gated
  • Voltage-Gated Sodium Channels

Grants and funding

This research was supported by the Australian Research Council (ARC) through its Special Research Initiative (SRI) in Bionic Vision Science and Technology grant to Bionic Vision Australia (BVA). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.