• Journal of Life Science
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• v.22 no.7
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• pp.863-870
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• 2012

Rhodopsin, a dim light photoreceptor, has been regarded as one of the model systems for the structural and functional study of G protein-coupled receptors (GPCRs). Constitutively active mutant GPCRs leading to the activation of heterotrimeric GDP/GTP-binding protein signaling in the absence of ligand binding are of interest for the study of the activation mechanism in GPCRs. The present study focused on the opsin mutant E134Q/M257Y, which showed a moderate level of constitutive activity and the formation of two distinct rhodopsin chromophores with absorption maxima of 500 nm and 380 nm, depending on the presence of an inverse agonist, 11-cis-retinal, and an agonist, all-trans-retinal, respectively. Reconstitution of the mutant rhodopsin upon incubation with different ratios of 11-cis-retinal and the all-trans-retinal, as well as upon sequential binding of the two retinals, indicated its preferential binding to 11-cis-retinal. The thermal stability of the 11-cis-retinal-bound form of the E134Q/M257Y mutant was lower than that of the mutants containing a single replacement but higher than that of the all-trans-retinal-bound forms. The mutant also showed a lower stability in its opsin state as compared with that of the wild-type opsin but had little effects on the binding affinity to 11-cis-retinal. Information obtained in this study will be helpful for analyzing the structural changes associated with the activation of rhodopsin and GPCRs.

• ETRI Journal
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• v.29 no.1
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• pp.59-69
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• 2007

We designed and fabricated a vision chip for edge detection with a $160{\times}120$ pixel array by using 0.35 ${\mu}m$ standard complementary metal-oxide-semiconductor (CMOS) technology. The designed vision chip is based on a retinal structure with a resistive network to improve the speed of operation. To improve the quality of final edge images, we applied a saturating resistive circuit to the resistive network. The light-adaptation mechanism of the edge detection circuit was quantitatively analyzed using a simple model of the saturating resistive element. To verify improvement, we compared the simulation results of the proposed circuit to the results of previous circuits.

• Molecules and Cells
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• v.46 no.7
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• pp.420-429
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• 2023

Age-related macular degeneration (AMD) is one of the leading causes of blindness in elderly individuals. However, the currently used intravitreal injections of anti-vascular endothelial growth factor are invasive, and repetitive injections are also accompanied by a risk of intraocular infection. The pathogenic mechanism of AMD is still not completely understood, but a multifactorial mechanism that combines genetic predisposition and environmental factors, including cellular senescence, has been suggested. Cellular senescence refers to the accumulation of cells that stop dividing due to the presence of free radicals and DNA damage. Characteristics of senescent cells include nuclear hypertrophy, increased levels of cell cycle inhibitors such as p16 and p21, and resistance to apoptosis. Senolytic drugs remove senescent cells by targeting the main characteristics of these cells. One of the senolytic drugs, ABT-263, which inhibits the antiapoptotic functions of Bcl-2 and Bcl-xL, may be a new treatment for AMD patients because it targets senescent retinal pigment epithelium (RPE) cells. We proved that it selectively kills doxorubicin (Dox)-induced senescent ARPE-19 cells by activating apoptosis. By removing senescent cells, the expression of inflammatory cytokines was reduced, and the proliferation of the remaining cells was increased. When ABT-263 was orally administered to the mouse model of senescent RPE cells induced by Dox, we confirmed that senescent RPE cells were selectively removed and retinal degeneration was alleviated. Therefore, we suggest that ABT-263, which removes senescent RPE cells through its senolytic effect, has the potential to be the first orally administered senolytic drug for the treatment of AMD.

• 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.

• 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.

• Journal of the Korea Institute of Information and Communication Engineering
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• v.9 no.7
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• pp.1594-1600
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• 2005

Recently many researches have been studied in the human vision model to solve the Wblem of the machine vision. Starting from research on the human visual system, first, we investigate the mechanisms of retina through physiological and biological evidence. In retina, input data was processed information processing that was data reduction edge detection, and emphasizing region. The processed image was recognized by region. In this paper, we proposed retinal algorithms that process data reduction and edge detection by the wavelet transform and emphasize region contrast. In experiments, the proposed model simulates processing the retina outputs in the levels and compares with outputs.

• The Korean Journal of Zoology
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• v.1 no.2
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• pp.17-24
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• 1958

Since Kesser first described in 1934 the functional change of the autonomic nervous system caused by certain visible rays many researchers have unanimously approved that animals flashed with a red visible ray develop parasympathicotony while those flashed with a blue visible ray develop sympathicotony. On the other hand through studies made by our colleagues it is now well known that the inner-movement of the retinal pigments of frogs is stimulated in sympathicotony and is in reverse inhibited in parasimpathicotony. It is almost evident that the mechanism by which the inner-movement of the retinal pigments is due to sympathicotony derived from the excessive secretion of adrenalin. In addition , through may recent experiments on the pharmacological action of various medicines on the retinal pigments reaction of tadpoles , ranging from the excessive secretion of adrenalin. In addition , through my recent experiments on the pharmacologtical action of various medicines on the retinal pigments reaction of tadploes, raging from every developmental stage , Ifound that the movement of the retinal pigments by adrenalin is predominant in the earlier developmental stages of taopoles around 11 mm of body length, whereas other medicines fail to give any responce to the retinal pigments in such an earlier stage. When tadpoles grown to body length of 15-16m the retinal pigments move to the complete light position while kept in adrenalin solution. Based on these facts it might be well to consider that if tadpoles were grown under the visible rays for a given period, they might show a functional change of the autonomic nervous system and thereby cause of certain change in the physciological phases of the retinal reaction. Experiments were undertaken to find this matter and also to discover the simultaneous effects of the visible radiations on the developmental process of tadpoles. The results summarized as follows ; 1. The longest wave of visible rav has an effective reaction on the growth of body length of taopoles, while the shortest wave of visible ray causes the same for the metamorphoric differentiation of tadpoles. 2. When keeping two groups of tadpoles the first group of 15 mm body length grown for the period of one week and the latter group of 20 mm body length grown for two weeks under the various visible rays. swimming in adrenalin solution, the inner-movement of the retinal pigment occurs in both groups. The movement of pigments of the first group is accelerated in a sequence of blue ray \ulcorner green ray > brown ray> red ray, and that of the latter group is also accelerated in a sequence of blue ray>green ray > brown ray and red ray. 3. When keeping tow groups of tadpoles, the first group of 20 mm body length grown for the period of two weeks, the latter group of 25 m body length grown for three wheeks, under the various visible rays in sunlight, the inner-movement of the retinal pigments occurs in both groups. The movement of pigments of the first group is accelerated in a sequence of blue ray> green ray>brown ray and red ray, and that of the latter group is also accelerated in a sequence of blue ray > brow ray>red ray. 4. In order words, there facts manifest that tadpoles grown under the various visible rays reveal functional disturbances of the autonomic nervous system, at the time of 15 mm body length by adrenalin solution, which is a unique indicator illustrating the status of sympathicotony, and at the time of 20 mm body length by sunlight. This means that the longest visible ray cause sympathicotony, while the shortest visible ray causes parasympathicotony.

• Journal of Photoscience
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• v.9 no.2
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• pp.51-54
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• 2002

We propose a novel mechanism (Twist Sharing Mechanism) for the cis-trans photoisomerization of rhodopsin, based on the molecular dynamics (MD) simulation study. New things devised in our simulations are (1) the adoption of Mt. Fuji potentials in the excited state for twisting of the three bonds C9=C10, C11=C12 and C13=14 which are modeled using the detailed ab initio quantum chemical calculations and (2) to use the rhodopsin structure which was resolved recently by the X-ray crystallographic study. As a result, we found the followings: Due to the intramolecular steric hindrance between 20-methyl and 10-H in the retinal chromophore, the C12-C13 and C10-C11 bonds are considerably twisted counterclockwise in rhodopsin, allowing only counterclockwise rotation of the C11 =C12 in the excited state. The movement of 19-methyl in rhodopsin is blocked by the surrounding three amino acids, Thr 118, Met 207 and Tyr 268, prohibiting the rotation of C9=C10. As a result only all-trans form of the chromophore is obtainable as a photoproduct. At the 90$^{\circ}$ twisting of C11=C12 in the course of photoisomerization, twisting energies of the other bonds amount to about 20 kcal/mol. If the transition state for the thermal isomerization is assumed to be similar to this structure, the activation energy for the thermal isomerization around C11=C12'in rhodopsin is elevated by about 20 kcal/mol and the thermal isomerization rate is decelerated by 10$\^$-14/ times than that of the retinal chromophore in solution, protecting photosignal from the thermal noise.

• Progress in Medical Physics
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• v.19 no.3
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• pp.157-163
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• 2008

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). $8{\times}8$ grid layout MEA (electrode diameter: $30{\mu}m$, electrode spacing: $200{\mu}m$, 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.

• Molecules and Cells
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• v.43 no.7
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• pp.632-644
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• 2020

The molecular mechanism underlying autophagy impairment in the retinal pigment epithelium (RPE) in dry age-related macular degeneration (AMD) is not yet clear. Based on the causative role of poly(ADP-ribose) polymerase 1 (PARP1) in RPE necrosis, this study examined whether PARP1 is involved in the autophagy impairment observed during dry AMD pathogenesis. We found that autophagy was downregulated following H₂O₂-induced PARP1 activation in ARPE-19 cells and olaparib, PARP1 inhibitor, preserved the autophagy process upon H₂O₂ exposure in ARPE-19 cells. These findings imply that PARP1 participates in the autophagy impairment upon oxidative stress in ARPE-19 cells. Furthermore, PARP1 inhibited autolysosome formation but did not affect autophagosome formation in H₂O₂-exposed ARPE-19 cells, demonstrating that PARP1 is responsible for impairment of late-stage autophagy in particular. Because PARP1 consumes NAD⁺ while exerting its catalytic activity, we investigated whether PARP1 impedes autophagy mediated by sirtuin1 (SIRT1), which uses NAD⁺ as its cofactor. A NAD⁺ precursor restored autophagy and protected mitochondria in ARPE-19 cells by preserving SIRT1 activity upon H₂O₂. Moreover, olaparib failed to restore autophagy in SIRT1-depleted ARPE-19 cells, indicating that PARP1 inhibits autophagy through SIRT1 inhibition. Next, we further examined whether PARP1-induced autophagy impairment occurs in the retinas of dry AMD model mice. Histological analyses revealed that olaparib treatment protected mouse retinas against sodium iodate (SI) insult, but not in retinas cotreated with SI and wortmannin, an autophagy inhibitor. Collectively, our data demonstrate that PARP1-dependent inhibition of SIRT1 activity impedes autophagic survival of RPE cells, leading to retinal degeneration during dry AMD pathogenesis.