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Kim Schaffrath, Sabine Diarra, Claudia Werner, Anna-Marina van der Meer, Inga Schulte-Noelke, Frank Muller, Sandra Johnen, Peter Walter; Modulation of electrical activity in the retina of the rd10 mouse model using neuroprotective drugs. Invest. Ophthalmol. Vis. Sci. 2017;58(8):242.
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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 electrical activity with oscillations between 3 and 7 Hz. In comparison to the wildtype retina, ganglion cells in the degenerated rd10 retina are electrically less excitable. We hypothesized that neuroprotective drugs (e.g., taurine, brain-derived neurotrophic factor, pigment epithelium-derived factor) could modulate the electrical activity of the surviving retinal ganglion cells. We want to analyze if the drugs can reduce or abolish the spontaneous rhythmic activity and investigate if they can improve the retinal responses to different stimulation patterns.
Retinas from rd10 mice aged P28 to P30 were isolated and placed on multielectrode arrays. Perfusion experiments were performed using the following standardized protocol: retinas were perfused (1) with ames’ medium, (2) with ames’ medium plus the neuroprotective drug and (3) with ames’ medium in order to analyze the reversibility of the drugs’ effect. Every step lasted for 30 minutes. To confirm the drugs’ effect, step 2 und 3 were repeated. During perfusion, multielectrode recordings were performed to analyze the spontaneous electrical activity as well as the activity induced by electrical stimulation with currents ranging from 20 to 80 µA. For statistical analysis, two-tailed student’s t-test and one-way ANOVA analysis were used.
The spontaneous oscillations of rd10 retinas showed a frequency of 7 Hz. The frequency could be shifted to 12 Hz (p<0,0001) by perfusion with 1 mM taurine. This effect was reversible and no significant difference between the first and second perfusion with taurine was observed. Additionally, a tendency that retinas perfused with taurine were slightly more excitable became apparent; however, this tendency is so far without any statistical significance.
Treatment with taurine could modulate the spontaneous oscillations and the excitability in degenerated rd10 retinas. The results are a first step towards the combined use of microelectrode array-based stimulation together with neuroprotective drugs to improve electrical activity in retinas affected by degenerative diseases.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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