Abstract
Retinal prostheses that are currently used to restore vision in patients suffering from retinal degeneration are not adjusted to the changes occurring during the remodeling process of the retina. Recent studies revealed abnormal rhythmic activity in the retina of genetic mouse models of retinitis pigmentosa. Here we describe this abnormal activity also in a pharmacologically-induced (MNU) mouse model of retinal degeneration. To investigate how this abnormal activity affects the excitability of retinal ganglion cells, we recorded the electrical activity from whole mounted retinas of rd10 mice and MNU-treated mice using a microelectrode array system and applied biphasic current pulses of different amplitude and duration to stimulate ganglion cells electrically. We show that the electrical stimulation efficiency is strongly reduced in degenerated retinas, in particular when abnormal activity such as oscillations and rhythmic firing of bursts of action potentials can be observed. Using a prestimulus pulse sequence, we could abolish rhythmic retinal activity. Under these conditions, the stimulation efficiency was enhanced in a few cases but not in the majority of tested cells. Nevertheless, this approach supports the idea that modified stimulation protocols could help to improve the efficiency of retinal prostheses in the future.
Highlights
Photoreceptor degenerations such as retinitis pigmentosa (RP) or others are often inherited diseases and the progressive loss of rods and cones in the outer retina lead to untreatable blindness
We show that irrespective of the type of degeneration the efficiency to drive retinal ganglion cells (RGCs) activity by electrical stimulation is much lower in the degenerated retina compared to wild type retina
We show for the first time a similar spontaneous activity in another model for retinal degeneration in which photoreceptor death has been induced pharmacologically by treatment with MNU
Summary
Photoreceptor degenerations such as retinitis pigmentosa (RP) or others are often inherited diseases and the progressive loss of rods and cones in the outer retina lead to untreatable blindness. The currently applied concepts of electrical retinal stimulation using implantable electrode arrays do not take into account that remodeling processes are occurring during the degeneration process in the inner retina and that they may cause changes in electrophysiological properties of the retina. Spontaneous activity and stimulation efficiency in degenerated retina. The persisting RGCs represent a target for electrical stimulation by retinal prostheses to elicit visual percepts [6]. Not all of these changes seem to directly depend on photoreceptor death because hyperactivity in rd emerges before rod degeneration starts [13, 15]
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