MACULAR SENSITIVITY CHANGE AFTER COMPLEMENTARY LASER THERAPY AFTER RANIBIZUMAB INTRAVITREAL INJECTION IN BRANCH RETINAL VEIN OCCLUSION.

Purpose: We examined the effect of ranibizumab with or without laser photocoagulation on retinal sensitivity in eyes with branch retinal vein occlusion.

Methods: Prospective randomized control study. Thirty patients with branch retinal vein occlusion received intravitreal injection of ranibizumab in a monthly pro re nata regimen.

Age-Related Maculopathy Susceptibility 2 and Complement Factor H Polymorphism and Intraocular Complement Activation in Neovascular Age-Related Macular Degeneration.

Purpose: To investigate the association of risk alleles in complement factor H (CFH) and age-related maculopathy susceptibility 2 (ARMS2) with complement activation products in the aqueous humor in eyes with neovascular age-related macular degeneration (nAMD) including polypoidal choroidal vasculopathy (PCV), retinal angiomatous proliferation (RAP), and pachychoroid neovasculopathy (PNV).

Design: Prospective, comparative, observational study.

Participants: Treatment-naïve patients with nAMD and cataract patients as controls.

Changes in complement activation products after anti-VEGF injection for choroidal neovascularization in age-related macular degeneration and pachychoroid disease.

We evaluated changes in the complement system resulting from anti-vascular endothelial growth factor (VEGF) in eyes with age-related choroidal neovascularization (CNV) including neovascular age-related macular degeneration, pachychoroid neovasculopathy, and polypoidal choroidal neovasculopathy. We measured the concentrations of the complement activation products (C3a, C4a), VEGF, and monocyte chemotactic protein-1 in the aqueous humor during intravitreal anti-VEGF injections for CNV. The VEGF level decreased significantly (P < 0.

Complement Activation Products and Cytokines in Pachychoroid Neovasculopathy and Neovascular Age-Related Macular Degeneration.

Purpose: To investigate the characteristics of complement activation products and angiogenic cytokines in the aqueous humor in eyes with pachychoroid neovasculopathy (PNV) and neovascular age-related macular degeneration (nAMD).

Methods: This was a prospective, comparative, observational study. All patients with choroidal neovascularization were classified as PNV without polyps, PNV with polyps (polypoidal choroidal vasculopathy [PCV]), or drusen-associated nAMD according to the presence or absence of pachychoroid features and soft drusen.

Anaphylatoxin concentration in aqueous and vitreous humor in the eyes with vitreoretinal interface abnormalities.

The complement system may be activated in the posterior segment of the eye with chorioretinal disease, which may be reflected to the concentration of anaphylatoxins in the aqueous humor. Little is known about the distribution of anaphylatoxins in the aqueous and vitreous humor. The aim of the present study was to investigate the distribution of anaphylatoxin concentration in the aqueous and vitreous humor of the eyes with idiopathic epiretinal membrane or idiopathic macular hole.

Semantic Segmentation of the Choroid in Swept Source Optical Coherence Tomography Images for Volumetrics.

The choroid is a complex vascular tissue that is covered with the retinal pigment epithelium. Ultra high speed swept source optical coherence tomography (SS-OCT) provides us with high-resolution cube scan images of the choroid. Robust segmentation techniques are required to reconstruct choroidal volume using SS-OCT images.

Hybrid Three-Dimensional Visualization of Choroidal Vasculature Imaged by Swept-Source Optical Coherence Tomography.

Purpose: To create hybrid three-dimensional (3D) models of the choroidal vasculature from swept-source optical coherence tomography (SS-OCT) angiography images and to evaluate the model's characteristics.

Methods: This study used prospective, noncomparative case series, including 21 eyes of 21 healthy individuals. The 6 × 6-mm macular area was imaged repeatedly to obtain two cube image sets.

Evidence for Activation of Lectin and Classical Pathway Complement Components in Aqueous Humor of Neovascular Age-Related Macular Degeneration.

Purpose: The complement system is activated via 3 different pathways; the lectin pathway (LP), classical pathway (CP), and alternative pathway. To investigate the possible roles for the LP or CP in the development of neovascular age-related macular degeneration (nAMD), we compared aqueous humor levels of complement proteins of the LP and CP between eyes with nAMD and those with cataract as controls.

Methods: Seventeen eyes from 17 patients with treatment-naïve nAMD and 9 eyes from 9 patients with cataract were studied.

Morphometrical evaluation of the choriocapillaris imaged by swept-source optical coherence tomography angiography.

Purpose: To assess the reproducibility of quantitative morphometrical evaluation of the choriocapillaris imaged with swept-source optical coherence tomography angiography (SS-OCTA).

Subjects And Methods: This observational, cross-sectional case series included 35 eyes of healthy individuals and 32 eyes of 32 patients. Two images of the fovea were taken using SS-OCTA with 3×3 mm squares.

[Method for MEA Data Analysis of Drug-treated Rat Primary Neurons and Human iPSC-derived Neurons to Evaluate the Risk of Drug-induced Seizures].

　Use of the microelectrode array (MEA) system to record spontaneous neuron activity from networks of cultured neurons has potential as a good risk evaluation method for drug-induced seizure events. Spontaneous electrical activity in neural networks consists of action potential spikes and organized patterns of action potential bursts. In both potentiated rodent primary neurons and human induced pluripotent stem cell (iPSC)-derived neurons, an epileptogenic response pattern manifests as a synchronized burst from spatially separated neurons.

Halofuginone enhances the chemo-sensitivity of cancer cells by suppressing NRF2 accumulation.

The KEAP1-NRF2 system regulates the cellular defence against oxidative and xenobiotic stresses. NRF2 is a transcription factor that activates the expression of cytoprotective genes encoding antioxidative, detoxifying and metabolic enzymes as well as transporters. Under normal conditions, KEAP1 represses NRF2 activity by degrading the NRF2 protein.

A new paradigm for drug-induced torsadogenic risk assessment using human iPS cell-derived cardiomyocytes.

Introduction: Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are anticipated to be a useful tool for conducting proarrhythmia risk assessments of drug candidates. However, a torsadogenic risk prediction paradigm using hiPSC-CMs has not yet been fully established.

Methods: Extracellular field potentials (FPs) were recorded from hiPSC-CMs using the multi-electrode array (MEA) system.

Electrophysiological Characteristics of Human iPSC-Derived Cardiomyocytes for the Assessment of Drug-Induced Proarrhythmic Potential.

The aims of this study were to (1) characterize basic electrophysiological elements of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) that correspond to clinical properties such as QT-RR relationship, (2) determine the applicability of QT correction and analysis methods, and (3) determine if and how these in-vitro parameters could be used in risk assessment for adverse drug-induced effects such as Torsades de pointes (TdP). Field potential recordings were obtained from commercially available hiPSC-CMs using multi-electrode array (MEA) platform with and without ion channel antagonists in the recording solution. Under control conditions, MEA-measured interspike interval and field potential duration (FPD) ranged widely from 1049 to 1635 ms and from 334 to 527 ms, respectively and provided positive linear regression coefficients similar to native QT-RR plots obtained from human electrocardiogram (ECG) analyses in the ongoing cardiovascular-based Framingham Heart Study.

[Multimodal Imaging of a Case of Acute Annular Outer Retinopathy].

Background: Acute annular retinopathy (AAOR) is a rare entity showing grayish spots with annular lesions. We report the clinical characteristics of a patient with AAOR derived by using multimodal imaging including spectral-domain optical coherence tomography (OCT), fundus autofluorescence (FAF), and an adaptive optics fundus camera. Case: A 56-year-old man who had fever one month and a half before presenting.

Sulforaphane reduces advanced glycation end products (AGEs)-induced inflammation in endothelial cells and rat aorta.

Background And Aims: Advanced glycation end products (AGEs)-receptor RAGE interaction evokes oxidative stress and inflammatory reactions, thereby being involved in endothelial cell (EC) damage in diabetes. Sulforaphane is generated from glucoraphanin, a naturally occurring isothiocyanate found in widely consumed cruciferous vegetables, by myrosinase. Sulforaphane has been reported to protect against oxidative stress-mediated cell and tissue injury.

CSAHi study: Evaluation of multi-electrode array in combination with human iPS cell-derived cardiomyocytes to predict drug-induced QT prolongation and arrhythmia--effects of 7 reference compounds at 10 facilities.

Introduction: Drug-induced QT prolongation is a major safety issue during drug development because it may lead to lethal ventricular arrhythmias. In this study, we evaluated the utility of multi-electrode arrays (MEA) with human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) to predict drug-induced QT prolongation and arrhythmia.

Methods: Ten facilities evaluated the effects of 7 reference drugs (E-4031, moxifloxacin, flecainide, terfenadine, chromanol 293B, verapamil, and aspirin) using a MED64 MEA system with commercially available hiPS-CMs.

Pigment epithelium-derived factor inhibits caveolin-induced interleukin-8 gene expression and proliferation of human prostate cancer cells.

Caveolin-1 (Cav), a primary protein component of caveolae, is overexpressed in prostate cancer, thereby promoting growth and metastasis of this tumor. By contrast, pigment epithelium-derived factor (PEDF) has been shown to inhibit tumor growth and metastasis, including that of prostate cancer, via its anti-angiogenic and anti-inflammatory effects. Although it was recently demonstrated that PEDF binds to Cav and blocks its pro-inflammatory actions in endothelial cells, it remains unclear whether PEDF also inhibits the tumor-promoting effects of Cav in cultured prostate cancer cells.

Foveal structure during the induction phase of anti-vascular endothelial growth factor therapy for occult choroidal neovascularization in age-related macular degeneration.

Purpose: To evaluate the efficacy of monthly injections of aflibercept and ranibizumab on foveal structure after three months, for the treatment of occult choroidal neovascularization (CNV) in age-related macular degeneration (AMD).

Methods: We retrospectively studied 103 eyes with treatment-naïve neovascular AMD with occult and no classic CNV. Seventy-four of 103 eyes were treated with ranibizumab (intravitreal ranibizumab injection [IVR] group); 29 eyes were treated with aflibercept (intravitreal aflibercept injection [IAI] group).

DNA Aptamer Raised against Advanced Glycation End Products Prevents Abnormalities in Electroretinograms of Experimental Diabetic Retinopathy.

Purpose: Abnormalities in electroretinograms (ERG), such as reduced amplitudes and delayed implicit times of a- and b-wave and oscillatory potentials (OPs), are one of the earliest features of diabetic retinopathy prior to obvious vascular changes in diabetic retinas. We have previously shown that serum levels of advanced glycation end products (AGEs) are correlated with a delayed latency of OPs in type 2 diabetic rats. However, the pathological role of AGEs in ERG abnormalities remains unclear.

Improvement of acquisition and analysis methods in multi-electrode array experiments with iPS cell-derived cardiomyocytes.

Introduction: Multi-electrode array (MEA) systems and human induced pluripotent stem (iPS) cell-derived cardiomyocytes are frequently used to characterize the electrophysiological effects of drug candidates for the prediction of QT prolongation and proarrhythmic potential. However, the optimal experimental conditions for obtaining reliable experimental data, such as high-pass filter (HPF) frequency and cell plating density, remain to be determined.

Methods: Extracellular field potentials (FPs) were recorded from iPS cell-derived cardiomyocyte sheets by using the MED64 and MEA2100 multi-electrode array systems.

Dipeptidyl peptidase-4 deficiency protects against experimental diabetic nephropathy partly by blocking the advanced glycation end products-receptor axis.

Advanced glycation end products (AGEs) and their receptor (RAGE) have a role in diabetic nephropathy. We have recently found that linagliptin, an inhibitor of dipeptidyl peptidase-4 (DPP-4), could inhibit renal damage in type 1 diabetic rats by suppressing the AGE-RAGE axis. However, it remains unclear whether DPP-4 deficiency could also have beneficial effects on experimental diabetic nephropathy.

Empagliflozin, an Inhibitor of Sodium-Glucose Cotransporter 2 Exerts Anti-Inflammatory and Antifibrotic Effects on Experimental Diabetic Nephropathy Partly by Suppressing AGEs-Receptor Axis.

Advanced glycation end products (AGEs) and receptor RAGE play a role in diabetic nephropathy. We have previously shown that increased glucose uptake into proximal tubular cells via sodium-glucose cotransporter 2 (SGLT2) stimulates oxidative stress generation and RAGE expression, thereby exacerbating the AGE-induced apoptosis in this cell type. However, the protective role of SGLT2 inhibition against the AGE-RAGE-induced renal damage in diabetic animals remains unclear.

Elevation of Serum Levels of Advanced Glycation End Products in Patients With Non-B or Non-C Hepatocellular Carcinoma.

Background: The prevalence of non-B or non-C hepatocellular carcinoma (NBNC-HCC) has been increasing all over the world. Advanced glycation end products (AGE) play a role in the pathogenesis of alcoholic liver injury or nonalcoholic steatohepatitis (NASH).

Methods: We examined here whether serum levels of AGE were elevated in NBNC-HCC patients compared with NASH subjects without HCC and investigated which anthropometric and clinical variables were independent determinants of AGE.