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Long-Sheng Fan, Jason Wolfe, Frank Yang, Grace Teng, C. L. Lee, Chih-Cheng Hsieh, KT Tang, Ming Wu, C.-H. Yang, Chung-May Yang; Mouse Retinal Ganglion Cell Responses to Sub-Retinal Electrical Excitation by High-Density Retinal Prosthesis Chips. Invest. Ophthalmol. Vis. Sci. 2012;53(14):5537.
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We previously reported high-density retinal prosthesis chips with arrays (from 64 to 4,096 pixels) of electrodes 10 μm in diameter and 30 μm in pitch using a 180 nm CMOS Image Sensor technology. Small electrodes typically face large impedance that might limit their total electrical output capability. To verify the in vitro efficacy of these high-density retinal prosthesis chips when used in sub-retinal excitation of RGC’s, we directly programmed these chips to generate biphasic current with amplitude up to +-50 μA, which will still allow operating a large array within the temperature-rise limitation.
Mouse retina tissue patches with bipolar cell side facing down are placed on the retinal prosthesis chips with a 30μm electrode pitch. Each of the microelectrodes is directly addressed and programmed through a Labview interface. Catholic-first biphasic electrical stimulations with variable amplitudes and pulse widths are used for stimulation, and loose patch and whole-cell patch clamp techniques are used to record the retinal ganglion cells responses on these arrays. Microelectrodes are first scanned individually, or in 2X2 groups using nominal values to find the electrical receptive field before varying other parameters in the RGC characterization, and the post stimulus time histograms (PSTH) are plotted for latency and threshold analysis. To verify that the RGC responses are not evoked through direct electrical excitations, RGC responses are recorded before and after application of 0.5 mM kynurenic acid or 2mM kynurenic acid, 100uM DNQX and 200uM APV.
It’s shown that a single 10 μm-sized electrode of the retinal prosthesis chip in the sub-retinal region is capable of inducing RGC spiking using a peak current of 40 μA which is within its driving capability. The RGC-spike-to-electrical-stimulus latency is more than 25 ms, which is comparable to that from light stimulation, and varying the electrical stimulation can evoke single or multiple spikes per sub-retinal stimulation. In the receptors blocking experiments, RGC cells fully lost electrical stimulus-driven response within a couple minutes of drug delivery, and recovered the electrical stimulus-driven responses after a 50-minute drug washout.
This study demonstrates the feasibility to evoke RGC spikes through retinal neural network in vitro by electrically stimulating retinal tissue from the sub-retinal region using high-density retinal prosthesis chips with 10 μm-sized electrodes 30 μm in pitch. These retinal prosthesis chips can evoke single RGC spikes, or multiple spikes that might be needed for psychological threshold of visual perception.
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