Article
Modulation of electrical activity in the retina of the rd10 mouse model using neuroprotective drugs
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Published: | November 30, 2017 |
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Purpose: The rd10 mouse is a commonly used animal model of retinal degenerative diseases, e.g., retinitis pigmentosa. In comparison to the wildtype retina, the rd10 retina shows spontaneous electrical activity with oscillations from 4 to 7 Hz and the ganglion cells are electrically less excitable. We hypothesized that neuroprotective drugs (e.g., taurine, pigment epithelium-derived factor (PEDF)) could modulate the electrical activity of the surviving retinal ganglion cells and analyzed if the drugs can reduce or abolish the spontaneous rhythmic activity.
Methods: Retinas from rd10 mice aged P28 to P31 were isolated and placed on multielectrode arrays (MEAs). Perfusion experiments were performed using the following standardized protocol: retinas were perfused with Ames’ medium (step 1), with Ames’ medium plus the neuroprotective drug (2) and with Ames’ medium (3) in order to analyze the reversibility of the drugs’ effect. Every step lasted for 30 minutes. To confirm the drugs’ effect, step 2 and 3 were repeated. During perfusion, MEA recordings were performed to analyze the spontaneous electrical activity.
Results: The oscillations of rd10 retinas showed a frequency of 5.8 +/- 0.5 Hz. Using perfusion with 1mM taurine, the oscillations could be abolished and the firing frequency was reduced from 94 to 32 Hz (averaged spike number per electrode). Both effects were reversible and reproducible. Using 200 µg/L PEDF, neither the firing frequency nor the frequency of the oscillations could be reduced.
Conclusions: Treatment with 1mM taurine could modulate the spontaneous oscillations in degenerated rd10 retinas, whereas 200µg/L PEDF showed no significant effect. The results are a first step towards the combined use of MEA-based stimulation together with neuroprotective drugs in order to improve electrical activity in retinas affected by degenerative diseases.
Acknowledgement: The study was supported by Pro Retina Stiftung and the DFG Grants WA-1472/6-3, JO-1263/1-3, MU-3036/3-3.