• Biomolecules & Therapeutics
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• v.27 no.5
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• pp.474-483
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• 2019

Vascular endothelial growth factor (VEGF) plays a pivotal role in pathologic ocular neovascularization and vascular leakage via activation of VEGF receptor 2 (VEGFR2). This study was undertaken to evaluate the therapeutic mechanisms and effects of the tetrapeptide Arg-Leu-Tyr-Glu (RLYE), a VEGFR2 inhibitor, in the development of vascular permeability and choroidal neovascularization (CNV). In cultured human retinal microvascular endothelial cells (HRMECs), treatment with RLYE blocked VEGF-A-induced phosphorylation of VEGFR2, Akt, ERK, and endothelial nitric oxide synthase (eNOS), leading to suppression of VEGF-A-mediated hyper-production of NO. Treatment with RLYE also inhibited VEGF-A-stimulated angiogenic processes (migration, proliferation, and tube formation) and the hyperpermeability of HRMECs, in addition to attenuating VEGF-A-induced angiogenesis and vascular permeability in mice. The anti-vascular permeability activity of RLYE was correlated with enhanced stability and positioning of the junction proteins VE-cadherin, ${\beta}$-catenin, claudin-5, and ZO-1, critical components of the cortical actin ring structure and retinal endothelial barrier, at the boundary between HRMECs stimulated with VEGF-A. Furthermore, intravitreally injected RLYE bound to retinal microvascular endothelium and inhibited laser-induced CNV in mice. These findings suggest that RLYE has potential as a therapeutic drug for the treatment of CNV by preventing VEGFR2-mediated vascular leakage and angiogenesis.

• Journal of Korea Multimedia Society
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• v.12 no.8
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• pp.1073-1081
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• 2009

In this paper, we proposed new method to enhance choroidal vessels by suppressing retina vessels brightness. It is well-known that CNV(choroidal neovascularization) is related with sight loss. The main feature of CNV is the occurrence of new vessels in choroid. Unfortunately, because retina vessels brightness is stronger than choroidal vessels brightness in ICGA(indocynanine green angiography) image, so that the choroidal vessels were hardly recognized. Therefore, for correct diagnosis, the choroidal vessels must be enhanced in ICGA image. The proposed enhancement method consists of 3 strategies. First, the retina vessels were detected by multi scale enhancement technique, hysteresis thresholding, KNN(Kth-nearest neighbor) classification method. And then, a retina vessel mask was generated from detection result. Next, the brightness of retina vessels was suppressed by the proposed conditional region erosion method and mask region until the mask region was vanished. Finally, the brightness of choroidal vessel was enhanced on processed image. Through an experiment, we had confirmed that the proposed method was robust and efficient.

• BMB Reports
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• v.51 no.7
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• pp.315-316
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• 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.

• Radiation Oncology Journal
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• v.25 no.2
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• pp.63-69
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• 2007

[ $\underline{Purpose}$ ]: We performed this prospective randomized study to evaluate the efficacy and the complications of radiotherapy for Subfoveal CNV in ARMD and to compare the treatment results at two dosages (14.4 Gy and 19.8 Gy). $\underline{Materials\;and\;Methods}$: 60 eyes of 55 patients were enrolled, and randomized into 14.4 Gy (31 eyes) or 19.8 Gy (29 eyes) groups. CT was used to plan the radiotherapy. All patients received radiotherapy with a 1.8 Gy daily dose using 4 MV photon. We categorized treatment results as improved, stable, or deteriorated based on visual acuity changes of more than 2 lines on the ETDRS chart. $\underline{Results}$: Median follow-up period was 33.5 months. At 12 months, visual acuity improved in 9 (16.7%), stable in 41 (75.9%), and aggravated in 4 (7.4%) of 54 evaluated eyes. At 24 months, 49 eyes (81.7%) were evaluated. Visual acuity improved in 6 (12.2%), was stable in 33 (67.4%), and deteriorated in 10 (20.4%). At 36 months, 37 eyes were evaluated. Six (16.2%) eyes were improved, 21 (56.8%) stable, and 10 (27.0%) deteriorated. No significant difference in response was observed between the 14.4 Gy and 19.8 Gy groups (Mantel-Haenszel $x^2=0.4756$). The proportion of eyes with a vision of $20/100{\leq}increased$ from 28.3% initially to 32.7% after 24 months of radiotherapy. There were no severe acute or chronic complications. $\underline{Conclusion}$: External beam radiotherapy with doses of 14.4 or 19.8 Gy may be an effective treatment for subfoveal CNV in ARMD. No dose-response relationships with respect to treatment response or toxicity were observed between the 14.4 Gy and 19.8 Gy groups.

• Journal of The Korean Ophthalmological Society
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• v.59 no.12
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• pp.1142-1151
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• 2018

Purpose: We assessed the visual and anatomical outcomes, and the safety profile of long-term intravitreal anti-vascular endothelial growth factor (VEGF) injections (aflibercept, ranibizumab, and bevacizumab) given to treat neovascular age-related macular degeneration (NAMD). Methods: We analyzed medical records collected over 7 years of treatment-naive NAMD patients who received outpatient clinic-based intravitreal anti-VEGF injections. All were treated employing either "treat-and-extend" or "as needed" protocols at the discretion of the retinal specialist. The number of injections, adverse events associated with injection, and measures of visual acuity (VA), central foveal thickness (CFT), and intraocular pressure (IOP) were recorded. Results: Overall, we assessed 196 eyes of 196 patients (average age $68.6{\pm}9.6years$; 77 females). Patients received an average of $17.3{\pm}13.5$ injections over $78.0{\pm}16.5months$ of clinical follow-up. The initial mean VA (logMAR) was $0.75{\pm}0.58$ and the CFT was $349.7{\pm}152.6{\mu}m$. Both parameters exhibited maximal improvements at the 6-month visit (p < 0.05). However, the clinical outcomes worsened over the 7-year clinical course; the best-corrected visual acuity (BCVA) was $0.91{\pm}0.78$ and the CFT was $284.5{\pm}105.8{\mu}m$ at 7 years. The BCVA at 7 years was significantly correlated with the initial BCVA. IOP-related events increased 11-fold and anterior chamber reactions increased 3-fold over the years, but no significant complications such as endophthalmitis were recorded. Conclusions: The use of intravitreal anti-VEGF agents was associated with initial visual improvements over 6 months but did not prevent the worsening of NAMD over 5 years. The BCVA at the initial visit was a strong predictor of the final BCVA. A more intensive injection schedule might improve long-term outcomes.