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.
Highlights
Current strategies to restore vision to those suffering from retinal degeneration are varied, ranging from re-growth of photoreceptors from stem cells, to using electrical stimulation to activate the remaining cells in the retina
We report that electrical stimulation elicits both intrinsic and extrinsic membrane potential changes in the majority of cells recorded
We sought to record directly from cells of the inner nuclear layer (INL) in the mouse retina during subretinal, external electrical stimulation, to assess the influence that these cells may have over the eventual output of the retina
Summary
Current strategies to restore vision to those suffering from retinal degeneration are varied, ranging from re-growth of photoreceptors from stem cells, to using electrical stimulation to activate the remaining cells in the retina. Technologies and techniques have advanced greatly over the years with several groups producing electrode arrays that can be implanted on, or near, the retina [2,3,4,5,6]. These aim to stimulate the cells remaining in the retina after photoreceptors are lost in diseases such as retinitis pigmentosa and macular degeneration. Despite the relative success of these projects it is still unknown exactly how electrical stimulation activates retinal neurons to produce perceived visual sensation
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