• 대한의용생체공학회:의공학회지
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• 제28권2호
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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.

• Molecules and Cells
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• 제46권7호
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• pp.441-450
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• 2023

β-Catenin (Ctnnb1) has been shown to play critical roles in the development and maintenance of epithelial cells, including the retinal pigment epithelium (RPE). Ctnnb1 is not only a component of intercellular junctions in the epithelium, it also functions as a transcriptional regulator in the Wnt signaling pathway. To identify which of its functional modalities is critically involved in mouse RPE development and maintenance, we varied Ctnnb1 gene content and activity in mouse RPE lineage cells and tested their impacts on mouse eye development. We found that a Ctnnb1 double mutant (Ctnnb1^dm), which exhibits impaired transcriptional activity, could not replace Ctnnb1 in the RPE, whereas Ctnnb1^Y654E, which has reduced affinity for the junctions, could do so. Expression of the constitutively active Ctnnb1^∆ex3 mutant also suppressed the development of RPE, instead facilitating a ciliary cell fate. However, the post-mitotic or mature RPE was insensitive to the loss, inactivation, or constitutive activation of Ctnnb1. Collectively, our results suggest that Ctnnb1 should be maintained within an optimal range to specify RPE through transcriptional regulation of Wnt target genes in the optic neuroepithelium.

• 생명과학회지
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• 제17권8호통권88호
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• pp.1068-1074
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• 2007

파브알부민(pa π albumin)은 망막의 다양한 세포타입에서 분포하고 있다. 본 연구팀은 이전연구에서 박쥐 망막의 내핵층에서의 파브알부민의 분포를 보고하였다. 현재 연구에서 본 연구팀은 한국관박쥐 (Rhinolophus ferrumequinum) 망막의 신경절세포층에 존재하는 파브알부민을 함유하는 신경세포를 규명하였고, 이들 세포의 분포양상을 조사하였다. 실험 결과,파브알부민의 면역반응성은 신경절세포층의 다수 세포에서 발견되었으며, 이들 세포는 주로 중간형 이상 크기의 세포체를 가지고 있었다. 조사된 세포체의 직경은 12.35 - 19.12 ${\mu}m$ 의 범위를 가지며 (n=166), 신경섬유층의 섬유 역시 염색되는 것으로 보아, 파브알부민을 함유하는 신경절세포는 대부분이 중간형이상 크기의 신경절세포임을 뒷받침하고 있다. NND (nearest neighbor distance) 분석을 통해서 본, 평균 NND는 59.57 에서 62.45 ${\mu}m$ 로 나타났으며, 평균 RI (regularity index) 는 2.95 ${\pm}$ 0.3 (mean${\pm}$s.d., n=4) 으로 계산되었다. 이를 종합해보면, 파브알부민은 한국관박쥐 망막의 신경절세포층에서 중간형이상 크기의 신경절세포에서 주로 발현하고 있으며, 이들은 규칙적인 배열을 가진 채 잘 조직화된 분포양상을 보여주고 있음을 알 수 있었다. 이러한 결과들은, 아직까지 명확하게 규명되어 있지 못한 박쥐의 시각에 대한 이해에 중요하게 적용될 수 있을 것이라고 사료된다.

• Journal of Nutrition and Health
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• 제38권2호
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• pp.96-103
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• 2005

It has been suggested that the elevated plasma homocysteine may lead to retinal dysfunction. We investigated the effects of plasma levels of homocysteine and folate on the retinal glial cells' injuries. Male Sprague-Dawley rats were raised either on a control diet or on an experimental diet containing 3.0 g/kg homocystine without folic acid for 10 weeks. Plasma homocysteine concentrations were measured by a HPLC-fluorescence detection method. Plasma folate and vitamin B/sub 12/ levels were analyzed by a radioimmunoassay. The response of Muller cells which are the principal glial cells of the retina was immunohistochemically examined using an antibody for vimentin, a cytoskeletal protein belonging to the family of intermediate filament. At 2 weeks, the homocystine diet induced a twofold increase in plasma homocysteine, and a concomitant increase in the expression of vimentin in the Muller cells' processes spanning from the inner to outer membranes of the retina indicating arterial degeneration. At 10 weeks, the homocystine diet induced a fourfold increase in plasma homocystine, but vimentin immunoreactivity in the retinas was similar in both groups. In conclusion, increased plasma homocysteine levels have influence on morphological and functional changes of Muller cells in the retina. (Korean J Nutrition 38(2): 96～103, 2005)

• BMB Reports
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• 제56권9호
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• pp.502-507
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• 2023

Photobiomodulation therapy has been proposed as a promising therapeutic approach for retinal degenerative diseases. However, its effect on the regenerative capacity in mammalian retina and its intracellular signalling mechanisms remain unknown. Here, we show that photobiomodulation with 670 nm light stimulates Müller glia cell cycle re-entry and dedifferentiation into a progenitor-like state in both the uninjured and injured retina. We also find that 670 nm light treatment inhibits the Hippo pathway, which is activated in Müller glia following NaIO₃-induced retinal injury. YAP, a major downstream effector of the Hippo signalling pathway was translocated into the nucleus of Müller glia along with YAP dephosphorylation in retina treated with 670 nm light. Deficiency of YAP attenuated Müller glia cell cycle re-entry and dedifferentiation. Our data reveal that the Hippo-YAP signalling pathway is associated with the photostimulatory effect on regenerative response in mammalian retina, and suggest a potential therapeutic strategy for retinal degenerative diseases.

• 대한의용생체공학회:의공학회지
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• 제30권4호
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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.

• 한국의학물리학회지:의학물리
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• 제18권1호
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• pp.20-26
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• 2007

망막질환에 의해 변성된 망막에서는 시냅스 조직의 구성이나 전기적 특성이 정상망막과는 크게 다를 것으로 예상된다. 그러므로 본 논문에서는 다채널기록법을 이용하여 정상 망막과 변성 망막에서 망막파형을 기록한 후 그 파형을 주성분 분석법과 독립성분분석법을 이용하여 비교 분석하였다. 주성분분석법은 망막파형 분석법으로 확립된 방법인 반면 독립성분분석법은 EEG 신호의 분석법으로는 확립된 방법이나 아직 망막파형 분석법으로 사용된 적이 없으므로 본 연구진이 최초로 적용하여 보았다. 본 연구진에 의해 프로그램된 독립성분분석법을 위한 toolbox를 사용하여 시공간적 분석을 실시한 결과 정상 마우스에서는 독립성분분석법 또한 주성분분석법과 같이 망막신경절세포 파형의 분석 방법으로서의 사용가능성을 발견하였다 그러나 rd/rd 마우스에서는 독립성분분석법으로 그린 공간지도상에서 다수의 강한 활성과 약한 활성이 혼재되어 나오는 복잡한 양상을 띄었다. 추후 어떠한 기전에 의해 변성망막의 공간지도가 이렇게 복잡한 양상을 띄는지에 관한 연구가 진행되어야 할 것으로 사료된다.

• Biomolecules & Therapeutics
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• 제17권2호
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• pp.175-180
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• 2009

Taurine is the most abundant free amino acid in the retina and transported into retina via taurine transporter (TauT) at the inner blood-retinal barrier (iBRB). In the present study, we investigated whether the taurine transport at the iBRB is regulated by oxidative stress or disease-like state in a conditionally immortalized rat retinal capillary endothelial cell line (TR-iBRB) used as an in vitro model of iBRB. First, [$^3H$]taurine uptake and efflux by TR-iBRB were regulated in the presence of extracellular $Ca^{2+}$. [$^3H$]Taurine uptake was inhibited and efflux was enhanced under $Ca^{2+}$ free condition in the cells. In addition, oxidative stress inducing agents such as tumor necrosis factor-$\alpha$ (TNF-$\alpha$), lipopolysaccharide (LPS), diethyl maleate (DEM) and glutamate increased [$^3H$]taurine uptake and decreased [$^3H$]taurine efflux in TR-iBRB cells. Whereas, 3-morpholinosydnonimine (SIN-1), which is known to NO donor decreased [$^3H$]taurine uptake. Lastly, TR-iBRB cells exposed to high glucose (25 mM) medium and the [$^3H$]taurine uptake was reduced about 20% at the condition. Also, [$^3H$]taurine uptake was decreased by cytochalasin B, which is known to glucose transport inhibitor. In conclusion, taurine transport in TR-iBRB cells is regulated diversely at extracellular $Ca^{2+}$, oxidative stress and hyperglycemic condition. It suggested that taurine would play a role as a retinal protector in diverse disease states.

• BMB Reports
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• 제42권7호
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• pp.456-461
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• 2009

Proteomic analyses of differentially expressed proteins in rat retinal ganglion cells (RGC-5) following S-nitrosoglutathione (GSNO), an NO donor, treatment were conducted. Of the approximately 314 protein spots that were detected, 19 were differentially expressed in response to treatment with GSNO. Of these, 14 proteins were up-regulated and 5 were down- regulated. Notably, an increase in GAPDH expression following GSNO treatment was detected in RGC-5 cells through Western blotting as well as proteomics. The increased GAPDH expression in response to GSNO treatment was accompanied by an increase in Herc6 protein, an E3 ubiquitin ligase. Moreover, GSNO treatment resulted in the translocation of GADPH from the cytosol to the nucleus and its subsequent accumulation. These results suggest that NO stress-induced apoptosis may be associated with the nuclear translocation and accumulation of GAPDH in RGC-5 cells.

• Molecules and Cells
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• 제44권3호
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• pp.168-178
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• 2021

The retinal pigment epithelium (RPE) forms a monolayer sheet separating the retina and choroid in vertebrate eyes. The polarized nature of RPE is maintained by distributing membrane proteins differentially along apico-basal axis. We found the distributions of these proteins differ in embryonic, post-natal, and mature mouse RPE, suggesting developmental regulation of protein trafficking. Thus, we deleted tumor susceptibility gene 101 (Tsg101), a key component of endosomal sorting complexes required for transport (ESCRT), in embryonic and mature RPE to determine whether ESCRT-mediated endocytic protein trafficking correlated with the establishment and maintenance of RPE polarity. Loss of Tsg101 severely disturbed the polarity of RPE, which forms irregular aggregates exhibiting non-polarized distribution of cell adhesion proteins and activation of epidermal growth factor receptor signaling. These findings suggest that ESCRT-mediated protein trafficking is essential for the development and maintenance of RPE cell polarity.