• Journal of Yeungnam Medical Science
• /
• v.10 no.1
• /
• pp.77-81
• /
• 1993

The clinical evaluation was done in eight eyes of four patients with bilateral branch retinal vein occlusion. The onset of age was from 36 to 65 years, and three patients were women. Hypertension was the most common associated systemic disease. Retinal neovascularization was complicated in six eyes, and five eyes had vitreous hemorrhage. The vitrectomy was performed in three eyes. We believe that branch retinal vein occlusion associated with hypertension should be followed carefully in the fellow eyes.

• Biomolecules & Therapeutics
• /
• v.27 no.5
• /
• pp.474-483
• /
• 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 Yeungnam Medical Science
• /
• v.8 no.1
• /
• pp.252-258
• /
• 1991

Majority of the eyes with subfoveal neovascular membrane lose the central vision. We observed two patients who regained significant central vision as the result of the involution of subfoveal neovascularization. On follow-up fundus examination, the subretinal lesions revealed grayish neovascular membranes stained with fluorescein, but did not show the fluid leakage. And subretinal hemorrhage and subretinal fluid were gradually resolved. We assumed that functioning retinal pigment epithelium within the macula and young age were the important factors of the spontaneous improvement of visual outcome.

• BMB Reports
• /
• v.51 no.7
• /
• 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.

• Medical Lasers
• /
• v.10 no.1
• /
• pp.22-30
• /
• 2021

Background and Objectives Ocular alkali burns cause severe damage to the ocular tissues and vision loss. Solcoseryl is a standardized calf blood extract that normalizes the metabolic disturbance and aids in maintaining the chemical and hormonal balance and has been used to treat burns in various tissues. This study examined the effects of Solcoseryl on a rat corneal alkali burn model. Materials and Methods Twenty rats were assigned randomly to four equal groups, including alkali burn, hyaluronic acid, Solcoseryl eyedrop, and Solcoseryl gel. A corneal alkali burn was induced by a NaOH-soaked paper disc. The treatments were given twice a day, every day. The wound area was measured after 24 and 48 hours, and the degree of neovascularization and corneal opacity were scored every week. The rats were sacrificed after three weeks for immunohistochemistry (IHC) to compare the level of inflammatory cytokines, IL-1β, IL-6, and TNF-α. The thickness of the retinal layers was compared to observe any changes in the retina. Results The use of Solcoseryl on corneal alkali burn accelerated wound healing with less neovascularization, greater opacity, and less cataract. IHC showed that the inflammation of the cornea was controlled by both the hyaluronic acid and Solcoseryl treatments. On the other hand, the inflammation had spread to the retina. When the dosage forms were compared, eyedrops were more effective on corneal inflammation, while the gel-type had a greater effect on retinal inflammation. Conclusion Solcoseryl was effective in accelerating the wound healing rate on a corneal alkali burn but could not prevent the spread of inflammation from the cornea to the retina. Eyedrops were more effective on inflammation in the cornea, and the gel was more effective in the retina.

• BMB Reports
• /
• v.47 no.11
• /
• pp.637-642
• /
• 2014

Sulodexide is a mixed glycosaminoglycan composed of heparin and dermatan sulfate. In this study, the anti-angiogenic effect of sulodexide was investigated using an oxygen-induced retinopathy (OIR) mouse model. The retinas of sham-injected OIR mice (P17) had a distinctive central area of nonperfusion, and this area was significantly decreased in sulodexide-injected mice. The number of neovascular tufts measured by SWIFT_NV and mean neovascular lumen number were significantly decreased in sulodexide-injected mice. Hyperbaric oxygen exposure resulted in increased levels of VEGF, MMP-2 and MMP-9, and when mice were treated with sulodexide, a dose-dependent reduction in VEGF, MMP-2 and MMP-9 levels was observed. Our results clearly demonstrate the anti-angiogenic effect of sulodexide and highlight sulodexide as a candidate supplementary substance to be used for the treatment of ocular pathologies that involve neovascularization.

• Parasites, Hosts and Diseases
• /
• v.49 no.2
• /
• pp.167-171
• /
• 2011

We report here the records of 10 consecutive Korean patients (10 eyes) with ocular toxoplasmosis which showed the typical clinical manifestations with seropositivity for Toxoplasma gondii specific IgG antibodies by micro-ELISA between 2006 and 2010. Nine patients were males and 1 was female; their age was $50.5{\pm}13.8$ years. The most common accompanying signs were vitritis (100%), anterior uveitis (70%), and scattered white deposit (80%). Pre-existing retinochoroidal scar was found in 1 (10%) patient. All patients received antiparasitic chemotherapy and systemic corticosteroid treatment, which resolved the presenting attack and recovered the visual acuity better than initial one in 9 patients and worse in 1. Optic atrophy, cataract, and retinal neovascularization were observed during the follow-up period and recurrence was detected in 3 eyes (30%) 6 to 20 months after the initial attack. In Korea, although rarely detected and reported, ocular toxoplasmosis needs more attention in clinical field of retinal diseases.

• Proceedings of the Korean Institute of Intelligent Systems Conference
• /
• 2003.09a
• /
• pp.372-375
• /
• 2003

The incidence of blindness resulting from diabetic retinopathy has significantly increased despite the intervention of insulin to control diabetes mellitus. Early signs are microaneurysms, exudates, intraretinal hemorrhages, cotton wool patches, microvascular abnormalities, and venous beading. Advanced stages include neovascularization, fibrous formations, preretinal and vitreous microhemorrhages, and retinal detachment. Microaneurysm count is important because it is an indicator of retinopathy progression. The purpose of this paper is to apply data mining to detect diabetic retinopathy patterns in routine fundus fluorescein angiography. Early symptoms are of principal interest and therefore the emphasis is on detecting microaneurysms rather than vessel tortuosity. The analysis does not involve image-recognition algorithms. Instead, mathematical filtering isolates microaneurysms, microhemorrhages, and exudates as objects of disconnected sets. A neural network is trained on their distribution to return fractal dimension. Hausdorff and box counting dimensions grade progression of the disease. The field is acquired on fluorescein angiography with resolution superior to color ophthalmoscopy, or on patterns produced by physical or mathematical simulations that model viscous fingering of water with additives percolated through porous media. A mathematical filter and neural network perform the screening process thereby eliminating the time consuming operation of determining fractal set dimension in every case.

• Journal of Microbiology and Biotechnology
• /
• v.17 no.6
• /
• 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.

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