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Kim Schaffrath, Sabine Diarra, Jana Gehlen, Frank Muller, Peter Walter, Sandra Johnen; Modulation of the electrical activity in degenerative retinas of rd10 mice using neuroprotective drugs. Invest. Ophthalmol. Vis. Sci. 2019;60(9):20.
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© ARVO (1962-2015); The Authors (2016-present)
The rd10 mouse is a commonly used animal model of retinal degenerative diseases, e.g., retinitis pigmentosa. The rd10 retina shows spontaneous oscillations between 4 to 7 Hz and its retinal ganglion cells (RGC) are less electrically excitable in comparison to the wildtype (wt) retina. We investigated, if different neuroprotective drugs, e.g., 2-aminoethanesulfonic acid (taurine), pigment epithelium-derived factor (PEDF), betaxolol and brimonidine, can modulate the spontaneous electrical activity of the surviving RGCs and if they can improve the responses to electrical stimulation.
Retinas from rd10 and wt mice were isolated and placed on multielectrode arrays (MEAs). Perfusion experiments were performed following a standardized protocol to analyze the reversibility of the drugs’ effect. Electrophysiological recordings registered the spontaneous electrical activity of RGCs and their responses to different square wave pulses.
The fluctuant oscillations in rd10 retinas showed a frequency of 5.8 ±0.5 Hz, whereas no oscillations were observed in wt retinas. Using 200 µg/L PEDF, 100 µM betaxolol or brimonidine, neither the mean spontaneous firing frequency nor the frequency of the oscillations were modulated. Perfusion with 1 mM taurine abolished the oscillations in retinas of young mice (P28-31), perfusion with 1.5 mM taurine in older rd10 mice. The stimulation efficiency, which was determined as the ratio of the firing frequency in a time window of 0.5 seconds after the stimulus and the firing frequency three seconds before stimulation, was increased during perfusion with taurine in comparison to perfusion with Ames medium alone. However, the mean spontaneous firing frequency decreased from 5.7 ± 5.1 Hz to 2.4 ± 3.9 Hz during taurine perfusion. All described effects were reversible and reproducible.
Treatment with 1 and 1.5 mM taurine abolished the oscillations and improved the stimulation efficacy in degenerated rd10 retinas, whereas PEDF, brimonidine and betaxolol showed no significant effect. The results are a first step towards the combined use of MEA-based stimulation together with neuroprotective drugs to improve the spontaneous electrical activity in degenerated retinas.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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