Model-based comparison of current flow in rod bipolar cells of healthy and early-stage degenerated retina
| Autor: | Ege Iseri, Gianluca Lazzi, Pragya Kosta, Javad Paknahad, Kyle Loizos, Bryan W. Jones, James R. Anderson, Crystal Sigulinsky, Rebecca L. Pfeiffer |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Retinal degeneration Retinal Bipolar Cells genetic structures Biology Photoreceptor cell Retina Article 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound 0302 clinical medicine Retinal Rod Photoreceptor Cells Retinitis pigmentosa medicine Connectome Animals Computer Simulation Membrane potential Neuronal Plasticity Neurodegeneration Retinal Degeneration Computational Biology Retinal medicine.disease Sensory Systems eye diseases Ophthalmology 030104 developmental biology medicine.anatomical_structure chemistry Synapses 030221 ophthalmology & optometry Neuron sense organs Rabbits Neuroscience Signal Transduction |
| Zdroj: | Exp Eye Res |
| ISSN: | 1096-0007 |
| Popis: | Retinal degenerative diseases, such as retinitis pigmentosa, are generally thought to initiate with the loss of photoreceptors, though recent work suggests that plasticity and remodeling occurs prior to photoreceptor cell loss. This degeneration subsequently leads to death of other retinal neurons, creating functional alterations and extensive remodeling of retinal networks. Retinal prosthetic devices stimulate the surviving retinal cells by applying external current using implanted electrodes. Although these devices restore partial vision, the quality of restored vision is limited. Further knowledge about the precise changes in degenerated retina as the disease progresses is essential to understand how current flows in retinas undergoing degenerative disease and to improve the performance of retinal prostheses. We developed computational models that describe current flow from rod photoreceptors to rod bipolar cells (RodBCs) in the healthy and early-stage degenerated retina. Morphologically accurate models of retinal cells with their synapses are constructed based on retinal connectome datasets, created using serial section transmission electron microscopy (TEM) images of 70 nm-thick slices of either healthy (RC1) or early-stage degenerated (RPC1) rabbit retina. The passive membrane and active ion currents of each cell are implemented using conductance-based models in the Neuron simulation environment. In response to photocurrent input at rod photoreceptors, the simulated membrane potential at RodBCs in early degenerate tissue is approximately 10–20 mV lower than that of RodBCs of that observed in wild type retina. Results presented here suggest that although RodBCs in RPC1 show early, altered morphology compared to RC1, the lower membrane potential is primarily a consequence of reduced rod photoreceptor input to RodBCs in the degenerated retina. Frequency response and step input analyses suggest that individual cell responses of RodBCs in either healthy or early-degenerated retina, prior to substantial photoreceptor cell loss, do not differ significantly. |
| Databáze: | OpenAIRE |
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