• 생명과학회지
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• 제22권7호
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• pp.863-870
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• 2012

세포막 단백질 중 가장 큰 family를 형성하는 G protein-coupled receptor (GPCR)는 세포 외부의 다양한 신호를 세포 내 G 단백질의 활성화를 통하여 전달한다. 외부 신호자극이 없는 조건에서도 활성을 나타내는 항활성 돌연변이(constitutively active mutants, CAM)는 GPCR 신호전달 이상으로 인한 질병 치료나 GPCR의 활성화 구조연구에 좋은 대상이다. 본 연구는 시각수용체 로돕신에서 약한 항활성을 보이는 CAM의 하나인 E134Q/M257Y를 대상으로, inverse agonist와 agonist 존재 하에서 형성하는 두 가지 chromophore의 특성을 연구하였다. 이 CAM은 11-cis-retinal과 all-trans-retinal 존재 하에서 각기 최대흡광도가 500 nm와 380 nm인 로돕신을 형성한다. 두 가지 retinal을 다양한 비로 혼합한 조건과 연속적으로 결합하는 조건 하에서 각 형태의 로돕신 형성을 조사한 결과 E134Q/M257Y mutant는 11-cis-retinal과 우선적으로 결합함을 보여준다. E134Q/M257Y mutant는 wild type 옵신에 비해 11-cis-retinal에 대한 친화도는 별다른 차이가 없으나 옵신과 로돕신 상태의 안정성이 낮음이 확인되었다. 본 연구 결과는 GPCR의 활성화 시 일어나는 부분적 구조변화에 대한 정보를 제공하고, 구조정보에 기반한 GPCR신호를 미세하게 조절하는 물질의 발굴이나 개발에 유용하게 이용될 것이다.

• ETRI Journal
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• 제29권1호
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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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• 제46권7호
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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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• 제27권2호
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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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• 제2권2호
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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.

• 한국정보통신학회논문지
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• 제9권7호
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• pp.1594-1600
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• 2005

기존의 기계시각의 문제점을 극복하기 위해 최근에는 인간시각의 모델에 관한 연구가 진행 중이다. 인간시각에 관한 연구의 시발점으로 생리학과 생물학적 연구를 바탕으로 망막의 메커니즘에 대해서 분석한다. 망막에서는 정보축약, 경계선검출, 영역대비강조 등 3가지 정보처리가 일어나며, 각 정보처리에 의해 가공된 영상은 뇌로 전달되어 인식하게 된다. 본 논문에서는 웨이블릿을 이용하여 정보축약과 경계선을 검출하고, 영역대비강조에 의한 망막의 메커니즘을 제안한다. 실험에서는 각 단계에서의 세포의 결과를 모의실험하고, 제안된 알고리즘에 의해 영역이 강조된 결과영상을 비교하였다.

• 한국동물학회지
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• 제1권2호
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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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• 제9권2호
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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.

• 한국의학물리학회지:의학물리
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• 제19권3호
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• pp.157-163
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• 2008

망막색소변성(retinitis pigmentosa: RP)과 연령관련 황반변성(age-related macular Degeneration: AMD)은 망막변성으로 인해 실명에 이르는 대표적인 질환이며 망막이식장치의 개발을 통해 치료될 수 있다고 간주되고 있다. 성공적인 망막이식장치 개발을 위하여 여러 가지 선결요소가 필요하지만 그 중 한 가지가 이식장치에 인가할 전기자극을 최적화하는 것이다. 변성망막의 전기적 특성은 정상 망막과 다르리라 예측되므로 우리는 장차 개발될 망막 이식장치에 인가할 전기자극 최적화를 위한 가이드라인을 제공하기 위해 정상 망막과 변성망막의 망막파형 차이에 관한 연구를 하였다. 망막을 분리한 후 망막절편을 신경절세포 층이 다채널전극의 표면을 향하게 하여 전극에 붙인다. In-vitro 상태에서 망막 신경절세포의 전기신호를 기록하기 위해 전극 직경: $30{\mu}m$, 전극간 거리: $200{\mu}m$, 전극 임피던스 1 kHz에서 50 $k{\Omega}$인 8행 8열의 다채널전극을 사용하였다. 생후 28일된 정상마우스(C57BL/6J 종)에서는 짧은 시간대(<2 ms)의 망막 스파이크만 기록되었다. rd/rd 마우스(C3H/HeJ 종)에서는 정상적인 스파이크뿐만 아니라 약 100 ms 의 시간대를 가지는 느린 파형이 같이 기록되었다. 우리는 rd/rd 마우스에서만 관찰되는 이 느린 파형의 기전을 알아보고자 여러 가지 시냅스억제제를 사용하였다. 이 느린 파형은 rd/rd 마우스에서 양극세포로부터 신경절세포로 들어오는 흥분성입력이 정상마우스보다 강화되었기 때문에 발생한 것으로 보인다. rd/rd 마우스에서 흥분성입력이 강화되는 여러 가능성 중에서 망막변성으로 인해 수평세포로부터 양극세포로 들어오는 억제성 입력이 소실됨으로 인해 결과적으로 양극세포로부터 신경절세포로 들어오는 흥분성입력이 강화되었을 가능성이 가장 높은 것으로 보인다.

• Molecules and Cells
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• 제43권7호
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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.