title: Modeling the response of ON and OFF retinal bipolar cells during electric stimulation.
abstract: Retinal implants allowing blind people suffering from diseases like retinitis pigmentosa and macular degeneration to regain rudimentary vision are struggling with several obstacles. One of the main problems during external electric stimulation is the co-activation of the ON and OFF pathways which results in mutual impairment. In this study the response of ON and OFF cone retinal bipolar cells during extracellular electric stimulation from the subretinal space was examined. To gain deeper insight into the behavior of these cells sustained L-type and transient T-type calcium channels were integrated in the synaptic terminals of reconstructed 3D morphologies of ON and OFF cone bipolar cells. Intracellular calcium concentration in the synaptic regions of the model neurons was investigated as well since calcium influx is a crucial parameter for cell-to-cell activity between bipolar cells and retinal ganglion cells. It was shown that monophasic stimulation results in significant different calcium concentrations in the synaptic terminals of ON and OFF bipolar cells. Intracellular calcium increased to values up to fourfold higher in the OFF bipolar model neuron in comparison to the ON bipolar cell. Furthermore, geometric properties strongly influence the activation of bipolar cells. Monophasic, biphasic, single and repetitive pulses with similar lengths, amplitudes and polarities were applied to the two model neurons.
authors.affiliation: Institute for Analysis and Scientific Computing, Vienna University of Technology, 1040 Vienna, Austria.
authors.forename: P
authors.initials: P
authors.lastname: Werginz
authors.affiliation: Center for Ophthalmology, University of Tübingen, 72076 Tübingen, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Benav
authors.affiliation: Center for Ophthalmology, University of Tübingen, 72076 Tübingen, Germany; Center for Integrative Neurosciences, University of Tübingen, 72076 Tübingen, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Zrenner
authors.affiliation: Institute for Analysis and Scientific Computing, Vienna University of Technology, 1040 Vienna, Austria. Electronic address: frank.rattay@tuwien.ac.at.
authors.forename: F
authors.initials: F
authors.lastname: Rattay
mesh_terms: D001369:Axons / Q000502:physiology; D001766:Blindness / Q000209:etiology / Q000503:physiopathology / Q000628:therapy*; D015220:Calcium Channels / Q000502:physiology; D004558:Electric Stimulation / Q000379:methods*; D057809:HEK293 Cells; D006801:Humans; D008564:Membrane Potentials / Q000502:physiology; D008954:Models, Biological; D051245:Retinal Bipolar Cells / Q000502:physiology*; D012174:Retinitis Pigmentosa / Q000150:complications / Q000503:physiopathology
chemical_list: D015220:Calcium Channels
keywords: Compartment model; Electric stimulation; Retinal bipolar cells; Retinal implant