16 research outputs found

    Electrically-evoked responses for retinal prostheses are differentially altered depending on ganglion cell types in outer retinal neurodegeneration caused by Crb1 gene mutation

    Get PDF
    BackgroundMicroelectronic prostheses for artificial vision stimulate neurons surviving outer retinal neurodegeneration such as retinitis pigmentosa (RP). Yet, the quality of prosthetic vision substantially varies across subjects, maybe due to different levels of retinal degeneration and/or distinct genotypes. Although the RP genotypes are remarkably diverse, prosthetic studies have primarily used retinal degeneration (rd) 1 and 10 mice, which both have Pde6b gene mutation. Here, we report the electric responses arising in retinal ganglion cells (RGCs) of the rd8 mouse model which has Crb1 mutation.MethodsWe first investigated age-dependent histological changes of wild-type (wt), rd8, and rd10 mice retinas by H&E staining. Then, we used cell-attached patch clamping to record spiking responses of ON, OFF and direction selective (DS) types of RGCs to a 4-ms-long electric pulse. The electric responses of rd8 RGCs were analyzed in comparison with those of wt RGCs in terms of individual RGC spiking patterns, populational characteristics, and spiking consistency across trials.ResultsIn the histological examination, the rd8 mice showed partial retinal foldings, but the outer nuclear layer thicknesses remained comparable to those of the wt mice, indicating the early-stage of RP. Although spiking patterns of each RGC type seemed similar to those of the wt retinas, correlation levels between electric vs. light response features were different across the two mouse models. For example, in comparisons between light vs. electric response magnitudes, ON/OFF RGCs of the rd8 mice showed the same/opposite correlation polarity with those of wt mice, respectively. Also, the electric response spike counts of DS RGCs in the rd8 retinas showed a positive correlation with their direction selectivity indices (r = 0.40), while those of the wt retinas were negatively correlated (r = −0.90). Lastly, the spiking timing consistencies of late responses were largely decreased in both ON and OFF RGCs in the rd8 than the wt retinas, whereas no significant difference was found across DS RGCs of the two models.ConclusionOur results indicate the electric response features are altered depending on RGC types even from the early-stage RP caused by Crb1 mutation. Given the various degeneration patterns depending on mutation genes, our study suggests the importance of both genotype- and RGC type-dependent analyses for retinal prosthetic research

    Real-time label-free quantitative monitoring of biomolecules without surface binding by floating-gate complementary metal-oxide semiconductor sensor array integrated with readout circuitry

    Get PDF
    We report a label-free field-effect sensing array integrated with complementary metal-oxide semiconductor (CMOS) readout circuitry to detect the surface potential determined by the negative charge in DNA molecules. For real-time DNA quantification, we have demonstrated the measurements of DNA molecules without immobilizing them on the sensing surface which is composed of an array of floating-gate CMOS transistors. This nonimmobilizing technique allows the continuous monitoring of the amount of charged molecules by injecting DNA solutions sequentially. We have carried out the real-time quantitative measurement of 19 bp oligonucleotides and analyzed its sensitivity as a function of pH in buffer solutions. (c) 2007 American Institute of Physics.open2

    Charge and dielectric effects of biomolecules on electrical characteristics of nanowire FET biosensors

    Get PDF
    The sensing mechanism of nanowire field effect transistor (NWFET) biosensors is investigated by taking into consideration both the charge and dielectric effects of biomolecules. The dielectric effect of the biomolecules is dominantly reflected in the linear regime, whereas the charge property is manifested in the subthreshold regime. The findings are supported by bio-experiments and numerical simulations. This study provides a rudimentary means of understanding interactions between biomolecules and NWFET biosensors

    Temporal properties of network-mediated responses to repetitive stimuli are dependent upon retinal ganglion cell type

    No full text
    OBJECTIVE: To provide artificially-elicited vision that is temporally dynamic, retinal prosthetic devices will need to repeatedly stimulate retinal neurons. However, given the diversity of physiological types of retinal ganglion cells (RGCs) as well as the heterogeneity of their responses to electric stimulation, temporal properties of RGC responses have not been adequately investigated. Here, we explored the cell type dependence of network-mediated RGC responses to repetitive electric stimulation at various stimulation rates. APPROACH: We examined responses of ON and OFF types of RGCs in the rabbit retinal explant to five consecutive stimuli with varying inter-stimulus intervals (10-1000 ms). Each stimulus was a 4 ms long monophasic sinusoidal cathodal current, which was applied epiretinally via a conical electrode. Spiking activity of targeted RGCs was recorded using a cell-attached patch electrode. MAIN RESULTS: ON and OFF cells had distinct responses to repetitive stimuli. Consistent with earlier studies, OFF cells always generated reduced responses to subsequent stimuli compared to responses to the first stimulus. In contrast, a new stimulus to ON cells suppressed all pending/ongoing responses from previous stimuli and initiated its own response that was remarkably similar to the response from a single stimulus in isolation. This previously unreported \u27reset\u27 behavior was observed exclusively and consistently in ON cells. These contrasts between ON and OFF cells created a range of stimulation rates (4-7 Hz) that maximized the ratio of the responses arising in ON versus OFF cells. SIGNIFICANCE: Previous clinical testing reported that subjects perceive bright phosphenes (ON responses) and also prefer stimulation rates of 5-7 Hz. Our results suggest that responses of ON cells are weak at high rates of stimulation (\u3e ∼7 Hz) due to the reset while responses of OFF cells are strong at low rates (\u3c ∼4 Hz) due to reduced desensitization, both reducing the ratio of ON to OFF responses. In combination with previous results indicating that responses in ON cells more closely match physiological patterns (Im and Fried 2015 J. Physiol. 593 3577-96), our results offer a potential reason for the user preference of intermediate rates (5-7 Hz)

    Non-rectangular waveforms are more charge-efficient than rectangular one in eliciting network-mediated responses of ON type retinal ganglion cells

    No full text
    OBJECTIVE: For individuals blinded by outer retinal degenerative diseases, retinal prostheses would be a promising option to restore sight. Unfortunately, however, the best performance of existing devices is still far removed from normal vision. One possible reason for the shortcoming is thought to be suboptimal stimulation conditions such as the waveform shape of electric stimulus. In this study, we explored the effects of varying waveforms on network-mediated responses arising in retinal ganglion cells (RGCs). APPROACH: We used a cell-attached patch clamp technique to record RGC spiking activities in the isolated mouse retina. ON alpha RGCs were targeted by soma size and their light responses to stationary spot flashes. Spiking in targeted RGCs was measured in response to an epiretinally-delivered cathodal current pulse in four waveforms: rectangular, center triangular, increasing and decreasing ramp shapes. Each waveform was tested at three durations (20, 10, and 5 ms) with adjusted amplitude for a range of total charges (50-400 nC). MAIN RESULTS: ON alpha RGCs always generated two bursts of spikes in responses to all stimuli conditions we tested. However, at a given charge, effects of differing waveforms were distinct in the two bursts. For the first burst, the increasing ramp was most effective among the four waveforms (p  \u3c  0.05 for all pairwise comparisons with other waveforms). For example, in responses arising from 20 ms-long stimuli, the increasing ramp evoked ~44% more spikes on average than the rectangular shape which is the typical choice of neural stimulation. Also, the rectangular stimulus evoked the weakest response in the delayed burst arising from pulses of every duration. For instance, 20 ms-long stimuli in the three non-rectangular waveforms showed ~23% or more increment in spike counts compared to response arising from the rectangular one; but there was no statistical difference in response magnitudes across the non-rectangular waveforms. SIGNIFICANCE: Although the rectangular waveform has been primarily used in retinal prostheses our results indicate that rectangular stimulus is not optimal for network-mediated responses of ON alpha RGCs. Instead, non-rectangular waveforms evoke stronger responses at a given charge, indicating higher charge-efficiency. Therefore, non-rectangular waveforms are expected to enhance clinical efficacy of retinal prostheses

    Electric stimulus duration alters network-mediated responses depending on retinal ganglion cell type

    No full text
    OBJECTIVE: To improve the quality of artificial vision that arises from retinal prostheses, it is important to bring electrically-elicited neural activity more in line with the physiological signaling patterns that arise normally in the healthy retina. Our previous study reported that indirect activation produces a closer match to physiological responses in ON retinal ganglion cells (RGCs) than in OFF cells (Im and Fried 2015 J. Physiol. 593 3677-96). This suggests that a preferential activation of ON RGCs would shape the overall retinal response closer to natural signaling. Recently, we found that changes to the rate at which stimulation was delivered could bias responses towards a stronger ON component (Im and Fried 2016a J. Neural Eng. 13 025002), raising the possibility that changes to other stimulus parameters can similarly bias towards stronger ON responses. Here, we explore the effects of changing stimulus duration on the responses in ON and OFF types of brisk transient (BT) and brisk sustained (BS) RGCs. APPROACH: We used cell-attached patch clamp to record RGC spiking in the isolated rabbit retina. Targeted RGCs were first classified as ON or OFF type by their light responses, and further sub-classified as BT or BS types by their responses to both light and electric stimuli. Spiking in targeted RGCs was recorded in response to electric pulses with durations varying from 5 to100 ms. Stimulus amplitude was adjusted at each duration to hold total charge constant for all experiments. MAIN RESULTS: We found that varying stimulus durations modulated responses differentially for ON versus OFF cells: in ON cells, spike counts decreased significantly with increasing stimulus duration while in OFF cells the changes were more modest. The maximum ratio of ON versus OFF responses occurred at a duration of ~10 ms. The difference in response strength for BT versus BS cells was much larger in ON cells than in OFF cells. SIGNIFICANCE: The stimulation rates preferred by subjects during clinical trials are similar to the rates that maximize the ON/OFF response ratio in in vitro testing (Im and Fried 2016a J. Neural Eng. 13 025002). Here, we determine the stimulus duration that produces the strongest bias towards ON responses and speculate that it will further enhance clinical effectiveness

    Non-fullerene acceptor based photoelectric material for retinal prosthesis

    No full text
    Abstract Microelectronic retinal implants can restore a useful level of artificial vision in photoreceptor-damaged retina. Previously commercialized retinal prostheses require transocular connection lines to an external power supply and/or for data transmission, which are unwieldy and may cause unwanted side effects, such as infections. A recently reported wireless device used a rigid silicon substrate. However, it had the potential for a long-term mechanical mismatch with soft retinal tissue. In this work, we used organic photovoltaic materials which can be fabricated on flexible substrates as well as be operated without any physical connection to the external world. The present study employed PCE10 as an active layer for retinal prosthetic application for the first time. Compared to previously studied organic photovoltaic materials used in retinal prosthesis research (such as P3HT), our PCE10 devices showed higher efficiency, providing a huge advantage in this field. When the PCE10 was blended with other non-fullerene acceptors achieving a ternary organic photovoltaic layer (PCE10:ITIC:Y6 blend), it showed lower reduction of photocurrent under same irradiation frequency condition. The fabrication method for our organic photovoltaic device was simple and easy to control its thickness. The fabricated devices showed adequate photocurrent to stimulate the retinal neurons with a smaller reduction in generated photocurrent during repeating stimuli compared to P3HT or PCE10 alone.Author names: Please confirm if the author names are presented accurately and in the correct sequence (given name, middle name/initial, family name). Author: Given name [Jae Young] Last name [Kim]. Author: Given name [Byung Chul] Last name [Lee].Yes, they are correct

    Preclinical study to improve microbubble-mediated drug delivery in cancer using an ultrasonic probe with an interchangeable acoustic lens

    No full text
    Abstract Focused ultrasound with microbubbles (FUS-MBs) has shown that it can lead to an efficient drug delivery system (DDS) involving the oscillation and destruction of the MB but is limited in drug delivery due to its narrow pressure field. However, unfocused ultrasound with MBs (UUS-MBs) and an interchangeable acoustic lens can tune and enhance the pressure field for MB destruction to overcome the disadvantages of FUS-MB DDSs. We designed a lens suitable for an ultrasound-phased array probe and studied the optimal treatment conditions for MB destruction in vitro through an optical imaging setup. The DDS effects were evaluated in a rat hepatoma model using doxorubicin (DOX) treatment. A concave lens with a radius of curvature of 2.6 mm and a thickness of 4 mm was selected and fabricated. UUS-MBs with the acoustic lens at 60 Vpp for 32 cycles and a PRF of 1 kHz could induce MB destruction, promoting the DDS even under fluidic conditions. In the animal experiment, the UUS-MBs in the acoustic lens treatment group had a higher concentration of DOX in the tumor than the control group. Our system suggests uses an acoustic lens to increase DDS effectiveness by providing sufficient ultrasound irradiation to the MBs
    corecore