Model-based comparison of current flow in rod bipolar cells of healthy and early-stage degenerated retina. (June 2021)

• Record Type: Journal Article
• Authors: Kosta, Pragya; Iseri, Ege; Loizos, Kyle; Paknahad, Javad; Pfeiffer, Rebecca L.; Sigulinsky, Crystal L.; Anderson, James R.; Jones, Bryan W.; Lazzi, Gianluca
• Is Part Of: Experimental eye research. Volume 207(2021)
• Publication Date: 2021-06
• Subjects: Degenerated retina -- Rod bipolar cells -- Rod pathways -- Computational modeling -- Neuronal modeling -- Retinal degeneration -- Retinitis pigmentosa -- Neurodegeneration; (RodBC) Rod bipolar cell -- (RC1) Retinal connectome 1 -- (RPC1) Retinal pathoconnectome 1 -- (RC1-RodBC) Rod bipolar cells of RC1 -- (RPC1-RodBC) Rod bipolar cells of RPC1; Ophthalmology -- Periodicals; Eye -- Periodicals; Œil -- Périodiques; Ophthalmology; Periodicals; Electronic journals; 612.8405
• DOI: 10.1016/j.exer.2021.108554
• Languages: English
• ISSNs: 0014-4835

Abstract

Abstract: 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. Highlights: Computational modeling of retinal cells from connectomes of a healthy and a degenerated retina. Simulations represent the current flow from rod photoreceptors to rod bipolar cells (RodBCs). Photocurrent input leads to lower membrane potential at degenerated RodBCs than healthy RodBCs. Despite altered morphologies, loss of rod inputs is the main reason for lower membrane potentials. Frequency response exhibit similar low pass filter effect for both healthy and degenerated RodBCs.