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Electrically Evoked Responses Of Retinal Ganglion Cells In Wild Type and Rd10 Mouse Retinas.

Daniel L. Rathbun1* and Archana Jalligampala1, 2
  • 1 Eberhard-Karls University, Tuebingen, Institute for Ophthalmic Research / Experimental Ophthalmology, Germany
  • 2 Eberhard-Karls University, Graduate School of Neural and Behavioral Sciences, International Max Planck Research School, Germany

Abstract
Over the years, retinal implants have been developed to restore limited functional vision in patients blinded by outer retinal diseases like retinitis pigmentosa (RP) and age–related macular degeneration through electrical stimulation of the surviving neurons. The most extensively characterized animal model is the rd1 mouse. Howev-er, the recently identified rd10 mouse, which has a relatively delayed onset and slower progression of degenera-tion may be a more appropriate model for human RP. To support ongoing efforts to optimize prosthetic retinal stimulation [Zrenner 2011], optimal stimulation paradigms need to be established for this new mouse line. Here we investigate retinal ganglion cell (RGC) responses to different stimulation paradigms in adult wt and rd10 mice.

Introduction
Retinitis pigmentosa (RP) and age-related macular degeneration (AMD) are two forms of outer retinal diseases which result in a substantial loss of photoreceptors. Although, the remaining inner retina undergoes some physiological and morphological changes, the characteristic cellular layering is still preserved, offering the opportunity to restore vision by electrical stimulation of the residual neurons via retinal implants. The most extensively characterized animal model is the rd1 mouse. However, the recently identified rd10 mouse, which has a relatively delayed onset and slower progression of degeneration, may be a more appropriate model for human RP. In order to support ongoing efforts to optimize prosthetic retinal stimulation, paradigms need to be established for this new mouse line. Here, we in-vestigate retinal ganglion cell (RGC) responses to elec-trical stimulation in adult wt and rd10 mice.

Materials and Methods
RGC spiking responses were recorded in vitro from patches of wild-type and rd10 retina using a planar multi-electrode (Multichannel Systems, Reutlingen, Germany). Prior to electrical stimulation, spontaneous activity was recorded. Stimuli were applied epiretinally via one of the 60 electrodes of a multielectrode array (MEA) while the remaining electrodes recorded electrically evoked responses (MC Rack, MC-Stim Multichannel Systems; Fig. 1 & 2). Stimuli consisted of square-wave, monophasic (either cathodic or anodic) constant-voltage pulses with varying voltages and durations. Stimulus randomization was employed to compensate for recording instability-induced biases that have been previously observed. The stored data were processed and analyzed offline (Offline Sorter, Plexon Inc, TX; Neuroexplorer, Nex Technologies; and Matlab) to generate rastergrams, peristimulus histograms, and stimulus-response curves.

Results
In agreement with recent reports, spontaneous activity was higher and more oscillatory in rd10 retina than in the wild-type [Goo 2011]. For the wt retina, we found pulse voltage and duration requirements that are in agreement with previously published reports. In both wt and rd10 cells, a dependence on duration was seen only for a few transitional voltages (near threshold; Fig. 3-5). Both above and below these voltages the influence of duration was not significant. A subset of cells demonstrated an asymmetric preference for either negative or positive voltage pulses (Fig. 6 & 7). Additionally, ganglion cell responsiveness decreased with increased interelectrode distance out to around 800µm from the site of stimulation. Finally some cells in rd10 retina showed an initial suppression of spontaneous activity upon epiretinal stimulation.

Conclusion
Our preliminary findings present one of the first examinations of electrical stimulation in rd10 retina. Based on these findings, we propose tentative stimulation parameters appropriate for activation of rd10 retina. The relevance of our results to the continued devel-opment of efficient stimulation protocols for retinal prostheses is examined.

Figure Legends
Fig. 1 Standard planar MEA (30µm diameter electrodes, 200µm interelectrode distance, Multichannel systems, Reutlingen, Germany).
Fig. 2 Simultaneous epiretinal stimulation and recording from the retina [image from Eckhorn 2001].
Fig. 3-5 Sample voltage-duration response functions for an rd10 retinal ganglion cell.
Fig. 6 & 7 Asymmetric voltage responses.3D plots showing asymmetric voltage responses to cathodic and anodic pulses in rd10 retinal ganglion cells.

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Acknowledgements

BMBF, KFZ, 01G1002
DFG EXC307,2011-07
Tübingen IZKF grant # F 1222724.1
Tistou and Charlotte Kerstan Foundation
This work has previously been presented at the MEA Meeting 2012, Reutlingen, Germany.

References

Eckhorn, R., Stett, A., Schanze, T., Gekeler, F., Schwahn, H., Zrenner, E., Wilms, M., Eger, M., and Hesse, L. (2001). Physiologische funktionsprüfungen von Retinaimplantaten an Tiermodellen. Ophthalmologe 98, 369-375.

Goo, Y., Ahn, K., Song, Y., Ahn, S., Han, S., Ryu, S., and Kim, K. (2011). Spontaneous oscillatory rhythm in retinal activities of two retinal degeneration (rd1 and rd10) mice. Korean J. Physiol. Pharmacol. 15, 415-422.

Zrenner, E., Bartz-Schmidt, K., Benav, H., Besch, D., Bruckmann, A., Gabel, V., Gekeler, F., Greppmaier, U., Harscher, A., Kibbel, S., Koch, J., Kusnyerik, A., Peters, T., Stingl, K., Sachs, H., Stett, A., Szurman, P., Wilhelm, B., and Wilke, R. (2011). Subretinal electronic chips allow blind patients to read letters and combine them to words. Proc. R. Soc. B, 278, 1489–1497.

Keywords: epiretinal stimulation, suppression of spontaneous activity

Conference: Bernstein Conference 2012, Munich, Germany, 12 Sep - 14 Sep, 2012.

Presentation Type: Poster

Topic: Sensory processing and perception

Citation: Rathbun DL and Jalligampala A (2012). Electrically Evoked Responses Of Retinal Ganglion Cells In Wild Type and Rd10 Mouse Retinas.. Front. Comput. Neurosci. Conference Abstract: Bernstein Conference 2012. doi: 10.3389/conf.fncom.2012.55.00084

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Received: 23 May 2012; Published Online: 12 Sep 2012.

* Correspondence: Dr. Daniel L Rathbun, Eberhard-Karls University, Tuebingen, Institute for Ophthalmic Research / Experimental Ophthalmology, Tuebingen, 72070, Germany, drathbu2@hfhs.org