• Journal of Biomedical Engineering Research
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• v.30 no.4
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• pp.347-354
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• 2009

For the reliable transmission of meaningful visual information using prosthetic electrical stimulation, it is required to develop an effective stimulation strategy for the generation of electrical pulse trains based on input visual information. The characteristics of neuronal activities of retinal ganglion cells (RGCs) evoked by electrical stimulation should be understood for this purpose. In this study, for the development of an optimal stimulation strategy for visual prosthesis, we analyzed the neuronal responses of RGCs in rd1 mouse, photoreceptor-degenerated retina of animal model of retinal diseases (retinitis pigmentosa). Based on the in-vitro model of epiretinal prosthesis which consists of planar multielectrode array (MEA) and retinal patch, we recorded and analyzed multiunit RGC activities evoked by amplitude-modulated electrical pulse trains. Two modes of responses were observed. Short-latency responses occurring at 3 ms after the stimulation were estimated to be from direct stimulation of RGCs. Long-latency responses were also observed mainly at 2 - 100 ms after stimulation and showed rhythmic firing with same frequency as the oscillatory background field potential. The long-latency responses could be modulated by pulse amplitude and duration. From the results, we expect that optimal stimulation conditions such as pulse amplitude and pulse duration can be determined for the successful transmission of visual information by electrical stimulation.

• Molecules and Cells
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• v.19 no.3
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• pp.382-390
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• 2005

Calcium-binding proteins are thought to play important roles in calcium buffering. The present study investigated the effects of ischemia and reperfusion on calbindin D28K, calretinin, and parvalbumin immunoreactivity in the ganglion cell layer of the rabbit. Rabbits were administered ischemic damage by increasing the intraocular pressure. After 60 and 90 min of ischemia, reperfusion (7 d) was allowed to occur. The b-wave of the electroretinogram (ERG) was reduced by more than 50% and almost 80% in retina given ischemia for 60 and 90 min, respectively. The oscillatory potential (OPs) wave was reduced approximately 50% at 60 min ischemia and 70% at 90 min ischemia. In both normal and ischemic-treated retina, calcium-binding protein immunoreactivity was seen in many cells in the ganglion cell layer. In eyes subjected to 60 min ischemia, there was a decrease of the density of calbindin D28K- (8.29%), calretinin- (14.44%), and parvalbumin- (26.83%) immunoreactive (IR) cells compared to the control retina. In eyes subjected to 90 min ischemia, there was a higher decrease of the density of calbindin D28K- (18.48%), calretinin- (33.59%), and parvalbumin- (54.26%) IR cells than at 60 min. Some calcium-binding protein-IR neurons, especially calretinin-IR neurons, showed aggregations that were abnormally packed together in retina subjected to ischemia for 90 min. The results show that calbindin D28K-, calretinin-, and parvalbumin-IR cells in the ganglion cell layer are susceptible to ischemic damage and reperfusion. The degree of reduction varied among different calcium-binding proteins and ischemic damage times. These results suggest that calbindin D28K-containing neurons are less susceptible to ischemic damage than calretinin- and parvalbumin-containing neurons in the ganglion cell layer of rabbit retina.

• The Korean Journal of Physiology and Pharmacology
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• v.13 no.6
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• pp.443-448
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• 2009

For successful visual perception by visual prosthesis using electrical stimulation, it is essential to develop an effective stimulation strategy based on understanding of retinal ganglion cell (RGC) responses to electrical stimulation. We studied RGC responses to repetitive electrical stimulation pulses to develop a stimulation strategy using stimulation pulse frequency modulation. Retinal patches of photoreceptor-degenerated retinas from rd1 mice were attached to a planar multi-electrode array (MEA) and RGC spike trains responding to electrical stimulation pulse trains with various pulse frequencies were observed. RGC responses were strongly dependent on inter-pulse interval when it was varied from 500 to 10 ms. Although the evoked spikes were suppressed with increasing pulse rate, the number of evoked spikes were >60% of the maximal responses when the inter-pulse intervals exceeded 100 ms. Based on this, we investigated the modulation of evoked RGC firing rates while increasing the pulse frequency from 1 to 10 pulses per second (or Hz) to deduce the optimal pulse frequency range for modulation of RGC response strength. RGC response strength monotonically and linearly increased within the stimulation frequency of 1~9 Hz. The results suggest that the evoked neural activities of RGCs in degenerated retina can be reliably controlled by pulse frequency modulation, and may be used as a stimulation strategy for visual neural prosthesis.

• Molecules and Cells
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• v.37 no.8
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• pp.613-619
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• 2014

The optic nerve often suffers regenerative failure after injury, leading to serious visual impairment such as glaucoma. The main inhibitory factors, including Nogo-A, oligodendrocyte myelin glycoprotein, and myelin-associated glycoprotein, exert their inhibitory effects on axonal growth through the same receptor, the Nogo-66 receptor (NgR). Oncomodulin (OM), a calcium-binding protein with a molecular weight of an ~12 kDa, which is secreted from activated macrophages, has been demonstrated to have high and specific affinity for retinal ganglion cells (RGC) and promote greater axonal regeneration than other known polypeptide growth factors. Protamine has been reported to effectively deliver small interference RNA (siRNA) into cells. Accordingly, a fusion protein of OM and truncated protamine (tp) may be used as a vehicle for the delivery of NgR siRNA into RGC for gene therapy. To test this hypothesis, we constructed OM and tp fusion protein (OM/tp) expression vectors. Using the indirect immunofluorescence labeling method, OM/tp fusion proteins were found to have a high affinity for RGC. The gel shift assay showed that the OM/tp fusion proteins retained the capacity to bind to DNA. Using OM/tp fusion proteins as a delivery tool, the siRNA of NgR was effectively transfected into cells and significantly down-regulated NgR expression levels. More importantly, OM/tp-NgR siRNA dramatically promoted axonal growth of RGC compared with the application of OM/tp recombinant protein or NgR siRNA alone in vitro. In addition, OM/tp-NgR siRNA highly elevated intracellular cyclic adenosine monophosphate (cAMP) levels and inhibited activation of the Ras homolog gene family, member A (RhoA). Taken together, our data demonstrated that the recombinant OM/tp fusion proteins retained the functions of both OM and tp, and that OM/tp-NgR siRNA might potentially be used for the treatment of optic nerve injury.

• Journal of information and communication convergence engineering
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• v.2 no.2
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• pp.132-137
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• 2004

Most of the current computer vision theories are based on hypotheses that are difficult to apply to the real world, and they simply imitate a coarse form of the human visual system. As a result, they have not been showing satisfying results. In the human visual system, there is a mechanism that processes information due to memory degradation with time and limited storage space. Starting from research on the human visual system, this study analyzes a mechanism that processes input information when information is transferred from the retina to ganglion cells. In this study, a model for the characteristics of ganglion cells in the retina is proposed after considering the structure of the retina and the efficiency of storage space. The MNIST database of handwritten letters is used as data for this research, and ART2 and SOM as recognizers. The results of this study show that the proposed recognition model is not much different from the general recognition model in terms of recognition rate, but the efficiency of storage space can be improved by constructing a mechanism that processes input information.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.5
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• pp.555-563
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• 2017

Electrical stimulation through retinal prosthesis elicits both short and long-latency retinal ganglion cell (RGC) spikes. Because the short-latency RGC spike is usually obscured by electrical stimulus artifact, it is very important to isolate spike from stimulus artifact. Previously, we showed that topographic prominence (TP) discriminator based algorithm is valid and useful for artifact subtraction. In this study, we compared the performance of forward backward (FB) filter only vs. TP-adopted FB filter for artifact subtraction. From the extracted retinae of rd1 mice, we recorded RGC spikes with $8{\times}8$ multielectrode array (MEA). The recorded signals were classified into four groups by distances between the stimulation and recording electrodes on MEA (200-400, 400-600, 600-800, $800-1000{\mu}m$). Fifty cathodic phase-$1^{st}$ biphasic current pulses (duration $500{\mu}s$, intensity 5, 10, 20, 30, 40, 50, $60{\mu}A$) were applied at every 1 sec. We compared false positive error and false negative error in FB filter and TP-adopted FB filter. By implementing TP-adopted FB filter, short-latency spike can be detected better regarding sensitivity and specificity for detecting spikes regardless of the strength of stimulus and the distance between stimulus and recording electrodes.

• The Korean Journal of Physiology and Pharmacology
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• v.15 no.6
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• pp.415-422
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• 2011

Previously, we reported that besides retinal ganglion cell (RGC) spike, there is ~10 Hz oscillatory rhythmic activity in local field potential (LFP) in retinal degeneration model, rd1 mice. The more recently identified rd10 mice have a later onset and slower rate of photoreceptor degeneration than the rd1 mice, providing more therapeutic potential. In this study, before adapting rd10 mice as a new animal model for our electrical stimulation study, we investigated electrical characteristics of rd10 mice. From the raw waveform of recording using $8{\times}8$ microelectrode array (MEA) from in vitro-whole mount retina, RGC spikes and LFP were isolated by using different filter setting. Fourier transform was performed for detection of frequency of bursting RGC spikes and oscillatory field potential (OFP). In rd1 mice, ~10 Hz rhythmic burst of spontaneous RGC spikes is always phase-locked with the OFP and this phase-locking property is preserved regardless of postnatal ages. However, in rd10 mice, there is a strong phase-locking tendency between the spectral peak of bursting RGC spikes (~5 Hz) and the first peak of OFP (~5 Hz) across different age groups. But this phase-locking property is not robust as in rd1 retina, but maintains for a few seconds. Since rd1 and rd10 retina show phase-locking property at different frequency (~10 Hz vs. ~5 Hz), we expect different response patterns to electrical stimulus between rd1 and rd10 retina. Therefore, to extract optimal stimulation parameters in rd10 retina, first we might define selection criteria for responding rd10 ganglion cells to electrical stimulus.

• Journal of Biomedical Engineering Research
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• v.28 no.2
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• pp.212-217
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• 2007

As a preliminary study for the development of electrical stimulation strategy of artificial retina, we set up a method fur the reconstruction of input intensity variation from retinal ganglion cell(RGC) responses. In order to estimate light intensity variation, we used an optimal linear filter trained from given stimulus intensity variation and multiple single unit spike trains from RGCs. By applying ON/OFF stimulation(ON duration: 2 sec, OFF duration: 5 sec) repetitively, we identified three functional types of ganglion cells according to when they respond to the ON/OFF stimulus actively: ON cell, OFF cell, and ON-OFF cell. Experiments were also performed using a Gaussian random stimulus and a binary random stimulus. The input intensity was updated once every 90 msec(i. e. 11 Hz) to present the stimulus. The result of reconstructing 11 Hz Gaussian and binary random stimulus was not satisfactory and showed low correlation between the original and reconstructed stimulus. In the case of ON/OFF stimulus in which temporal variation is slow, successful reconstruction was achieved and the correlation coefficient was as high as 0.8.

• The Korean Journal of Physiology
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• v.27 no.2
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• pp.163-174
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• 1993

Vertebrate retinal neurons, like brain tracts farm complex synaptic relations in the enter and inner plexiform layers which ape equivalent to the central nervous system nuclei. The effects of $\gamma-aminobutyric$ acid(GABA) and glycine on retinal neurons were explored to discern the mechanisms of action of neurotransmitters. Experiments were performed in the superfused retina-eyecup preparation of the channel catfish, Ictalurus punctatus, using intracellular electrophysiological techniques. The roles of GABA and glycine as inhibitory neurotransmitters are well established in the vertebrate retina. But, we found that the depolarizing action of GABA and glycine on third-order neurons in the catfish retina. GABA and glycine appeared to act on retinal ueurons based on the observations that (1) effects on photoreceptors were not observed, (2) horizontal cells were either hyperpolarized $({\sim}33%)$ or depolarized $({\sim}67%)$, (3) bipolar cells were all hyperpolarized (4) amacrine and ganglion cells were either hyperpolarized $({\sim}37%)$ or depolarized $({\sim}63%)$, (5) GABA and glycine may be working to suppress presynaptic inhibition. The results suggest that depolarization of third-order neurons by GABA and glycine is due to at least two mechanisms; a direct postsynaptic effect and an indirect effect. Therefore, in the catfish retina, a mechanism of presynaptic inhibition or disinhibition including the direct postsynaptic effect may exist in the third-order neurons.

• Applied Microscopy
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• v.42 no.3
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• pp.142-146
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• 2012

Doublecortin (DCX) is a microtuble-associated protein that is required for the migration of immature neuroblasts within the chick and mammalian brain. Although it is generally thought that DCX is expressed only in the neuroblasts, some mature neurons maintain DCX expression; for example, horizontal cells in adult rat retina. In this study, we demonstrate that retinal neural progenitors in the early embryonic stage of the chick also expressed DCX, as do developing ganglion cells and horizontal cells in later stages of development. These findings raise the possibility of a role for DCX in retinal neural progenitors, before they become specialized into neuroblasts in the chick.