ABSTRACT
Retinal prostheses are being developed to restore vision for the blind with retinal diseases such as retinitis pigmentosa (RP) or age-related macular degeneration (AMD). Among the many issues for prosthesis development, stimulation encoding strategy is one of the most essential electrophysiological issues. The more we understand the retinal circuitry how it encodes and processes visual information, the greater it could help decide stimulation encoding strategy for retinal prosthesis. Therefore, we examined how retinal ganglion cells (RGCs) in in-vitro retinal preparation act together to encode a visual scene with multielectrode array (MEA). Simultaneous recording of many RGCs with MEA showed that nearby neurons often fired synchronously, with spike delays mostly within 1 ms range. This synchronized firing - narrow correlation - was blocked by gap junction blocker, heptanol, but not by glutamatergic synapse blocker, kynurenic acid. By tracking down all the RGC pairs which showed narrow correlation, we could harvest 40 functional connectivity maps of RGCs which showed the cell cluster firing together. We suggest that finding functional connectivity map would be useful in stimulation encoding strategy for the retinal prosthesis since stimulating the cluster of RGCs would be more efficient than separately stimulating each individual RGC.
Subject(s)
Fires , Gap Junctions , Heptanol , Kynurenic Acid , Macular Degeneration , Neurons , Prostheses and Implants , Retinal Diseases , Retinal Ganglion Cells , Retinaldehyde , Retinitis Pigmentosa , Synapses , Track and Field , Vision, Ocular , Visual ProsthesisABSTRACT
Retinal prosthesis is regarded as the most feasible method for the blind caused by retinal diseases such as retinitis pigmentosa or age-related macular degeneration. One of the prerequisites for the success of retinal prosthesis is the optimization of the electrical stimuli applied through the prosthesis. Since electrical characteristics of degenerate retina are expected to differ from those of normal retina, we investigated differences of the retinal waveforms in normal and degenerate retina to provide a guideline for the optimization of electrical stimulation for the upcoming prosthesis. After isolation of retina, retinal patch was attached with the ganglion cell side facing the surface of microelectrode arrays (MEA). 8x8 grid layout MEA (electrode diameter: 30micrometer, electrode spacing: 200micrometer, and impedance: 50 k omega at 1 kHz) was used to record in-vitro retinal ganglion cell activity. In normal mice (C57BL/6J strain) of postnatal day 28, only short duration (<2 ms) retinal spikes were recorded. In rd/rd mice (C3H/HeJ strain), besides normal spikes, waveform with longer duration (~100 ms), the slow wave component was recorded. We attempted to understand the mechanism of this slow wave component in degenerate retina using various synaptic blockers. We suggest that stronger glutamatergic input from bipolar cell to the ganglion cell in rd/rd mouse than normal mouse contributes the most to this slow wave component. Out of many degenerative changes, we favor elimination of the inhibitory horizontal input to bipolar cells as a main contributor for a relatively stronger input from bipolar cell to ganglion cell in rd/rd mouse.
Subject(s)
Animals , Mice , Electric Stimulation , Electrodes , Ganglion Cysts , Macular Degeneration , Microelectrodes , Prostheses and Implants , Retina , Retinal Diseases , Retinal Ganglion Cells , Retinaldehyde , Retinitis Pigmentosa , Visual ProsthesisABSTRACT
It is expected that synaptic construction and electrical characteristics in degenerate retina might be different from those in normal retina. Therefore, we analyzed the retinal waveform recorded with multielectrode array in normal and degenerate retina using principal component analysis (PCA) and independent component analysis (ICA) and compared the results. PCA is a well established method for retinal waveform while ICA has not tried for retinal waveform analysis. We programmed ICA toolbox for spatiotemporal analysis of retinal waveform. In normal mouse, the MEA spatial map shows a single hot spot perfectly matched with PCA-derived ON or OFF ganglion cell response. However in rd/rd mouse, the MEA spatial map shows numerous hot and cold spots whose underlying interactions and mechanisms need further investigation for better understanding.