• 대한안과학회지
• /
• 제59권12호
• /
• pp.1142-1151
• /
• 2018

목적: 삼출 나이관련황반변성에 대한 유리체내 항혈관내피성장인자 주사 치료의 장기 결과를 알아보고자 한다. 대상과 방법: 삼출 나이관련황반변성 진단 후 treat-and-extend 또는 as needed 방법으로 7년 이상 유리체내 항혈관내피성장인자 주사 치료를 시행 받은 환자들에 대한 후향적 의무기록 분석을 시행하였다. 주사 횟수, 최대교정시력 및 중심망막두께 등을 평가하였으며, 장기간 주사 치료에 따른 부작용 여부를 같이 조사하였다. 결과: 총 196명의 196안을 분석하였다(평균 나이 $68.6{\pm}9.6$세, 여성 77명). 평균 $78.0{\pm}16.5$개월 경과관찰하였고, 해당 기간 동안 평균 $17.3{\pm}13.5$회의 유리체내주사가 시행되었다. 치료 전 측정한 최대교정시력은 평균 $0.75{\pm}0.58$ logMAR, 중심망막두께는 $349.7{\pm}152.6{\mu}m$였고, 6개월째 두 수치 모두 최대 호전을 보였으나(p<0.05), 이후 점차 악화 소견을 보이며 7년째 최대교정시력 $0.91{\pm}0.78$ logMAR, 중심망막두께 $284.5{\pm}105.8{\mu}m$로 확인되었다. 주사 후 7년째 시력은 치료 전 시력과 강한 양의 상관관계를 보였다. 장기간 주사 동안 총 11회의 안압상승 및 3회의 전방 내 염증 증가 소견이 있었으나 안내염 등의 심각한 부작용은 관찰되지 않았다. 결론: 삼출 나이관련황반변성에서 유리체내 항혈관내피성장인자 주사 치료 후 초기 6개월간의 최대 시력 호전이 있었으나 5년 이상 경과 시 지속적인 시력 저하를 막지 못하였다. 진단 당시 시력이 장기 시력예후와 관련된 중요 예측 인자로 판단되며 적극적인 유리체 내주사 치료를 통해 더 나은 장기 시력 결과를 기대해 볼 수 있다.

• Clinical and Experimental Pediatrics
• /
• 제58권7호
• /
• pp.239-244
• /
• 2015

The complement system is part of the innate immune response and as such defends against invading pathogens, removes immune complexes and damaged self-cells, aids organ regeneration, confers neuroprotection, and engages with the adaptive immune response via T and B cells. Complement activation can either benefit or harm the host organism; thus, the complement system must maintain a balance between activation on foreign or modified self surfaces and inhibition on intact host cells. Complement regulators are essential for maintaining this balance and are classified as soluble regulators, such as factor H, and membrane-bound regulators. Defective complement regulators can damage the host cell and result in the accumulation of immunological debris. Moreover, defective regulators are associated with several autoimmune diseases such as atypical hemolytic uremic syndrome, dense deposit disease, age-related macular degeneration, and systemic lupus erythematosus. Therefore, understanding the molecular mechanisms by which the complement system is regulated is important for the development of novel therapies for complement-associated diseases.

• Journal of Microbiology and Biotechnology
• /
• 제17권6호
• /
• pp.1024-1030
• /
• 2007

We investigated the human apolipoprotein E2 (apoE2) transgenic mouse as an animal model system for age-related macular degeneration (AMD). Transgenic mice expressing human apoE2 and C57BL/6J mice were fed normal chow or a high-fat diet for 4 weeks. Eyes were collected from the mice and lipid deposits in retinal pigment epithelium (RPE) were assessed using electron microscopy. The expressions of apoE, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and pigment-epithelium derived factor (PEDF), which are molecular markers for angiogenesis, were assessed with immunohistochemistry. Eyes from apoE2 mice, regardless of diet, contained lipid accumulation in RPE under electron microscopy, whereas control C57BL/6J eyes did not. Lipid accumulation was found predominantly in the RPE and the Bruch's membrane and increased in the eyes of apoE2 mice after one month of a high-fat diet ($8{\pm}2\;per\;50{\mu}m^2$ for normal chow and $11{\pm}2\;per\;50\;{\mu}m^2,\;p<0.05)$. ApoE expression was similar in the apoE2 and control mice; however, VEGF and bFGF were overexpressed in the retinal pigment epithelium of apoE2 eyes compared with control eyes, and PEDF expression was slightly decreased. These expression patterns of VEGF, bFGF, and PEDF suggest angiogenesis is progressing in apoE2 eyes. In conclusion, the eyes of apoE2 mice develop typical lipid accumulations, a common characteristic of AMD, making them a suitable animal model for AMD. The expression profile of VEGF and bFGF on the retinal pigment epithelium suggests that apoE2 may induce neovascularization by altering angiogenic cytokines.

• BMB Reports
• /
• 제51권7호
• /
• pp.315-316
• /
• 2018

Genome engineering with clustered regularly interspaced short palindromic repeats (CRISPR) system can be used as a tool to correct pathological mutations or modulate gene expression levels associated with pathogenesis of human diseases. Owing to well-established local administration methods including intravitreal and subretinal injection, it is relatively easy to administer therapeutic genome engineering machinery to ocular tissues for treating retinal diseases. In this context, we have investigated the potential of in vivo genome engineering as a therapeutic approach in the form of ribonucleoprotein or CRISPR packaged in viral vectors. Major issues in therapeutic application of genome engineering include specificity and efficacy according to types of CRISPR system. In addition to previous platforms based on ribonucleoprotein and CRISPR-associated protein 9 derived from Campylobacter jejuni, we evaluated the therapeutic effects of a CRISPR RNA-guided endonuclease derived from Lachnospiraceae bacterium ND2006 (LbCpf1) in regulating pathological angiogenesis in an animal model of wet-type age-related macular degeneration. LbCpf1 targeting Vegfa or Hif1a effectively disrupted the expression of genes in ocular tissues, resulting in suppression of choroidal neovascularization. It was also notable that there were no significant off-target effects in vivo.

• 한국안광학회지
• /
• 제17권1호
• /
• pp.91-97
• /
• 2012

목적: 본 연구는 노인성 황반변성(age-related macular degeneration, AMD)의 병인으로 잘 알려진 A2E의 광산화가 자외선 차단렌즈나 brown 착색렌즈에 의해 억제되는가를 알아보고자 하였다. 방법: 두 분자의 all-trans-retinal과 한 분자의 ethanolamine을 합성하여 만든 A2E에 청색광(420~470 nm, $94mW/cm^2$)을 3분 동안 조사하여 광산화를 유도하였다. UV 차단 및 brown 착색 안경렌즈의 A2E의 광산화 저해 효과는 광산화되지 않고 남아있는 A2E의 흡광도와 HPLC chromatogram 분석을 통하여 확인하였다. 결과: 자외선 차단렌즈는 청색광 조사로 유발되는 A2E의 광산화를 억제하지 못하였다. 반면 Brown 착색렌즈에서는 가시광선 차단율이 15%인 경우 A2E의 광산화율에는 별차이가 없었지만, 55%와 86% 차단된 렌즈에서는 각각 9.98%, 16.55%의 A2E 광산화 억제 효과를 보였다. HPLC로 분석한 잔존 A2E량을 확인해 보면 렌즈로 차단하지 않은 A2E의 잔존량은 $199.29{\pm}26.53{\mu}M$ 이었으나, 55% 차단율을 가진 brown 렌즈는 $264.58{\pm}31.91{\mu}M$, 86% 차단율을 가진 렌즈에서는 $402.93{\pm}26.68{\mu}M$의 A2E 잔존량을 보여 A2E 광산화 억제효과가 있음을 확인하였다. 반면, 자외선 차단렌즈의 경우에는 잔존량 분석에서도 광산화 억제효과가 없는 것으로 나타났다. 결론: 본 연구결과를 통하여 brown 착색 안경렌즈는 노인성 황반변성의 원인물질인 A2E의 광산화를 억제하는 효과가 있는 것으로 알 수 있었다.

• Molecules and Cells
• /
• 제43권7호
• /
• pp.632-644
• /
• 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.

• Molecules and Cells
• /
• 제46권7호
• /
• pp.420-429
• /
• 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.

• 대한영양사협회학술지
• /
• 제27권2호
• /
• pp.77-91
• /
• 2021

This study was conducted to investigate the effect of the differences in nutrient intakes on the onset of eye disease in the ophthalmic disease group vs. the normal group. The analysis method of this study was performed by adjusting age and gender. The daily caloric intake was 1,672.1±26.4 kcal in the ophthalmic disease group which was significantly lower than the 2,041.5±13.6 kcal intake in the normal group (P=0.006). The intake of proteins (P=0.015) and carbohydrates (P=0.000) was significantly lower in the ophthalmic disease group than in the normal group. The incidence of eye diseases was found to decrease by about 0.79 (95% CI: 0.74~0.83) times as the NAR index of protein was increased, followed by 0.79 (95% CI: 0.64~0.98) times with an increase in niacin consumption. In this study, income, BMI, smoking, alcohol consumption, and quality of life were considered as the confounding variables related to eye disease, along with age and gender, but did not lead to show significant results. It was found that the ophthalmic disease group had an unbalanced nutritional intake compared to the normal group. Therefore, we conclude that nutrition education is necessary to ensurebalanced eating habits for management and prevention of degeneration after the onset of eye diseases.

• 한국멀티미디어학회논문지
• /
• 제22권11호
• /
• pp.1269-1279
• /
• 2019

In medical image analysis, segmentation is considered as a vital process since it partitions an image into coherent parts and extracts interesting objects from the image. In this paper, we consider automatic segmentations of OCT retinal images to find six layer boundaries using convolutional neural networks. Segmenting retinal images by layer boundaries is very important in diagnosing and predicting progress of eye diseases including diabetic retinopathy, glaucoma, and AMD (age-related macular degeneration). We applied well-known CNN architecture for general image segmentation, called Segnet, U-net, and CNN-S into this problem. We also proposed a shortest path-based algorithm for finding the layer boundaries from the outputs of Segnet and U-net. We analysed their performance on public OCT image data set. The experimental results show that the Segnet combined with the proposed shortest path-based boundary finding algorithm outperforms other two networks.

• The Korean Journal of Physiology and Pharmacology
• /
• 제12권6호
• /
• pp.307-314
• /
• 2008

Retinal prostheses are being developed to restore vision for the blind with retinal diseases such as retinitis pigmentosa (RP) or age-related macular degeneration (AMD). Among the many issues for prosthesis development, stimulation encoding strategy is one of the most essential electrophysiological issues. The more we understand the retinal circuitry how it encodes and processes visual information, the greater it could help decide stimulation encoding strategy for retinal prosthesis. Therefore, we examined how retinal ganglion cells (RGCs) in in-vitro retinal preparation act together to encode a visual scene with multielectrode array (MEA). Simultaneous recording of many RGCs with MEA showed that nearby neurons often fired synchronously, with spike delays mostly within 1 ms range. This synchronized firing - narrow correlation - was blocked by gap junction blocker, heptanol, but not by glutamatergic synapse blocker, kynurenic acid. By tracking down all the RGC pairs which showed narrow correlation, we could harvest 40 functional connectivity maps of RGCs which showed the cell cluster firing together. We suggest that finding functional connectivity map would be useful in stimulation encoding strategy for the retinal prosthesis since stimulating the cluster of RGCs would be more efficient than separately stimulating each individual RGC.