Nucleobindin-2 Mediates Transforming Growth Factor-ß1-Driven Phenotypes in Zinc Finger E-Box Binding Homeobox 1-High Uterine Carcinosarcoma.

Epithelial-mesenchymal transition is a hallmark of uterine carcinosarcoma (UCS). Here, shotgun proteomics analysis used to identify biomarkers associated with blebbistatin-mediated epithelial-mesenchymal transition in UCS indicated up-regulation of nucleobindin-2 (NUCB2) in endometrial carcinoma (Em Ca) cells. Expression of N-cadherin, Snail, Slug, and ZEB1 was reduced in NUCB2 knockout Em Ca cells, whereas ZEB1, Twist1, and vimentin were up-regulated in NUCB2-overexpressing Em Ca cells. NUCB2 knockout reduced cell proliferation and migration, whereas NUCB2 overexpression had the opposite effect. Treatment of Em Ca cells with transforming growth factor (TGF)-ß1 dramatically altered morphology toward a fibroblastic appearance; concomitantly, expression of NUCB2 and ZEB1 increased. The NUCB2 promoter was also activated by transfection of Smad2. In UCS tissues, NUCB2 expression was significantly higher in sarcomatous compared with carcinomatous components, which was consistent with increased TGF-ß1 mRNA expression in stromal and sarcomatous components compared with carcinomatous components. In addition, NUCB2 score correlated positively with ZEB1 and vimentin scores, whereas ZEB1 score correlated positively with Slug and vimentin scores and inversely with the E-cadherin score. Collectively, these data indicate that TGF-ß-dependent up-regulation of NUCB2 and ZEB1 contributes to the phenotypic characteristics of sarcomatous components in UCS.

Influence of dispersion slope on the diagnosis of liver fibrosis by the shear wave in metabolic dysfunction-associated steatotic liver disease.

AIM: Shear wave (SW) elastography is used to evaluate metabolic dysfunction-associated steatotic liver disease (MASLD) pathophysiology. Increased elasticity due to fibrosis and increased viscosity due to necrosis and inflammation affect SW. Assessing fibrosis, the most prognostically relevant pathology, is critical. Viscosity is evaluated using the dispersion slope (DS); however, cut-off values that affect SW values are unclear. We compared the ultrasound imaging parameters (SW for viscoelasticity; DS for viscosity) with pathological findings. METHODS: Patients (n = 159) who underwent liver biopsy and SW and DS assessments at our hospital were included. Fibrosis stage and inflammation grade cut-off values were calculated from SW, DS, and liver biopsy results using receiver operating characteristic curves. Cases in which liver biopsy results were inconsistent with SW results were used to determine the effect of viscosity on SW values. DS was examined in the Correct and Incorrect Diagnosis groups, which were categorized based on the concordance between SW and liver biopsy results. Dispersion slope cut-off values between the two groups were calculated. RESULTS: Fibrosis stage cut-off values by SW (m/s) were: ≥F2, 1.62; ≥F3, 1.74; and F4, 1.97. Inflammation grade cut-off values by DS (m/s/kHz) were: ≥A1, 11.6; ≥A2, 14.5; and A3, 16.1. The Correct/Incorrect Diagnosis groups had 25/70 patients. The DS cut-off value for both groups was 13.2 m/s/kHz. CONCLUSIONS: Shear wave and DS are useful for evaluating liver fibrosis and inflammation in MASLD. For DS > 13.2 m/s/kHz, SW may be affected by the increased viscosity owing to inflammation. In such patients, caution should be used when determining/interpreting values.

Roles of lipocalin-type and hematopoietic prostaglandin D synthases in mouse retinal angiogenesis.

Normal angiogenesis is essential for retinal development and maintenance of visual function in the eye, and its abnormality can cause retinopathy and other eye diseases. Prostaglandin D2 is an anti-angiogenic lipid mediator produced by lipocalin-type PGD synthase (L-PGDS) or hematopoietic PGD synthase (H-PGDS). However, the exact role of these PGD synthases remains unclear. Therefore, we compared the roles of these synthases in murine retinal angiogenesis under physiological and pathological conditions. On postnatal day (P) 8, the WT murine retina was covered with an elongated vessel. L-PGDS deficiency, but not H-PGDS, reduced the physiological vessel elongation with sprouts increase. L-PGDS expression was observed in endothelial cells and neural cells. In vitro, L-PGDS inhibition increased the hypoxia-induced vascular endothelial growth factor expression in isolated endothelial cells, inhibited by a prostaglandin D2 metabolite, 15-deoxy-Δ12,14 -PGJ2 (15d-PGJ2) treatment. Pericyte depletion, using antiplatelet-derived growth factor receptor-ß antibody, caused retinal hemorrhage with vessel elongation impairment and macrophage infiltration in the WT P8 retina. H-PGDS deficiency promoted hemorrhage but inhibited the impairment of vessel elongation, while L-PGDS did not. In the pericyte-depleted WT retina, H-PGDS was expressed in the infiltrated macrophages. Deficiency of the D prostanoid receptor also inhibited the vessel elongation impairment. These results suggest the endogenous role of L-PGDS signaling in physiological angiogenesis and that of H-PGDS/D prostanoid 1 signaling in pathological angiogenesis.

Silver(I) Coordination Polymer Ligated by Bipyrazole Me4bpzH2, [Ag(X)(Me4bpzH2)] (X = CF3CO2- and CF3SO3-, Me4bpzH2 = 3,3',5,5'-Tetramethyl-4,4'-bipyrazole): Anion Dependent Structures and Photoluminescence Properties.

Coordination polymers of transition metal ions are fascinating and important to coordination chemistry. One of the ligands known to form particularly interesting coordination polymers is 3,3',5,5'-tetramethyl-4,4'-bipyrazole (Me4bpzH2). Group 11 metal(I) ion coordination polymers, other than those of copper(I), are relatively easy to handle because of their low reactivity towards dioxygen and moisture. However, the known silver(I) coordination polymers often have poor solubility in common solvents and so cannot be easily analyzed in solution. By using a tetramethyl substituted bipyrazole ligand, we have synthesized more soluble silver(I) complexes that contain the trifluoromethyl group in the coordinated ions CF3CO2- and CF3SO3- in [Ag(CF3CO2)(Me4bpzH2)] and [Ag(CF3SO3)(Me4bpzH2)]. We determined both structures by single-crystal X-ray analysis at low temperatures and compared them in detail. Moreover, we investigated the solution behavior of these coordination polymers by 1H-NMR, IR, Raman, UV-Vis spectroscopies, and their low-temperature, solid-state photoluminescence. The high-energy band at ~330 nm corresponded to ligand-centered (bipyrazole) fluorescence, and the low-energy band at ~400 nm to ligand-centered phosphorescence resulting from the heavy atom effect.

Mosquito method based polymer tapered waveguide as a spot size converter.

We create a compact low-loss spot-size converter (SSC) which utilizes a tapered core polymer optical waveguide with circular cross-sectional graded-index (GI) core using the Mosquito method we developed. First, we theoretically analyze the mutual diffusion between the core and cladding monomers, which is a feature unique to the Mosquito method when forming GI cores. The monomer diffusion effect depends on the initial core diameter that is dispensed by a microdispenser and the diffusion time before UV curing: in a small core the monomer diffuses more rapidly than in a large core. Using this diffusion dependence on the initially dispensed core diameter, it is theoretically found that a tapered polymer waveguide based SSC can adiabatically convert the mode-field diameter between 4.0 and 8.6 µm at a 1550-nm wavelength waveguide as short as 4 mm. Next, the tapered waveguide based SSC with the designed structure is experimentally fabricated using the Mosquito method, and we confirm an 8-mm long tapered waveguide with an insertion loss of 1.83dB functions as a SSC that converts the MFD from 4.7 µm to 7.5 µm at 1550-nm wavelength.

Physiologically Based Pharmacokinetic Models Predicting Renal and Hepatic Concentrations of Industrial Chemicals after Virtual Oral Doses in Rats.

Recently developed high-throughput in vitro assays in combination with computational models could provide alternatives to animal testing. The purpose of the present study was to model the plasma, hepatic, and renal pharmacokinetics of approximately 150 structurally varied types of drugs, food components, and industrial chemicals after virtual external oral dosing in rats and to determine the relationship between the simulated internal concentrations in tissue/plasma and their lowest-observed-effect levels. The model parameters were based on rat plasma data from the literature and empirically determined pharmacokinetics measured after oral administrations to rats carried out to evaluate hepatotoxic or nephrotic potentials. To ensure that the analyzed substances exhibited a broad diversity of chemical structures, their structure-based location in the chemical space underwent projection onto a two-dimensional plane, as reported previously, using generative topographic mapping. A high-throughput in silico one-compartment model and a physiologically based pharmacokinetic (PBPK) model consisting of chemical receptor (gut), metabolizing (liver), central (main), and excreting (kidney) compartments were developed in parallel. For 159 disparate chemicals, the maximum plasma concentrations and the areas under the concentration-time curves obtained by one-compartment models and modified simple PBPK models were closely correlated. However, there were differences between the PBPK modeled and empirically obtained hepatic/renal concentrations and plasma maximal concentrations/areas under the concentration-time curves of the 159 chemicals. For a few compounds, the lowest-observed-effect levels were available for hepatotoxicity and nephrotoxicity in the Hazard Evaluation Support System Integrated Platform in Japan. The areas under the renal or hepatic concentration-time curves estimated using PBPK modeling were inversely associated with these lowest-observed-effect levels. Using PBPK forward dosimetry could provide the plasma/tissue concentrations of drugs and chemicals after oral dosing, thereby facilitating estimates of nephrotoxic or hepatotoxic potential as a part of the risk assessment.

A Robust Model for Prediction of U(VI) Adsorption onto Ferrihydrite Consistent with Spectroscopic Observations.

A robust model that can predict the adsorption behavior of U(VI) on ferrihydrite under a wide range of environmental conditions was developed with the aid of an extended triple-layer model. X-ray absorption spectroscopic observations from previous studies showed that the predominant U(VI) surface species on ferrihydrite was commonly a bidentate inner-sphere species under ambient CO2 conditions. Previous surface complexation models, however, could not predict U(VI) surface speciation because of the lack of sufficient macroscopic adsorption datasets with which to estimate the surface complexation reaction. In this study, we obtained U(VI) adsorption data at U(VI) concentrations of 10nM under a wide range of pH, ionic strength, and solid concentrations in NaNO3 solutions with/without atmospheric CO2. We determined the stoichiometries of the U(VI) adsorption reactions and the equilibrium constants with the adsorption data and the U(VI) hydroxyl constants recently estimated from direct luminescence measurements. A single set of equilibrium constants for the reactions could reproduce reasonably well the reported adsorption datasets obtained under a wide range of pH values (2-12), U(VI) concentrations (10-8 to 10-4 M), ionic strengths (0.004-0.5), and CO2 partial pressures (<10-6 to 10-1.7 atm). The model could also predict all U(VI) surface speciation consistent with previous spectroscopic observations under a wide range of solution conditions.

Effect of Manual Upper Eyelid Elevation on Intraocular Pressure Measurement by Four Different Tonometers.

SIGNIFICANCE: This study is the first to show that the manual upper eyelid elevation (manual UEE) that is commonly used to prevent disruption of the IOP measurement due to blinking or upper eyelid contact with the tip of the tonometer does not affect the IOP values. PURPOSE: We investigated whether manual UEE affects the IOP readings using three rebound tonometers (Icare TA01i, Icare PRO, and Icare ic100) and Goldmann applanation tonometry (GAT). METHODS: One eye was measured for 101 patients (56 eyes of primary open-angle glaucoma patients and 45 healthy subjects). The IOPs were measured without and with manual UEE. Each IOP was measured twice; the measurement order using the tonometers was randomly selected. In addition, palpebral fissure height (distance between the upper and lower eyelids) was measured. RESULTS: The IOPs without manual UEE were 12.1 ± 2.9, 13.3 ± 2.7, 11.7 ± 2.9, and 16.0 ± 3.2 mmHg (Icare TA01i, Icare PRO, Icare ic100, and GAT), and those with manual UEE were 12.3 ± 3.0, 13.3 ± 2.8, 11.7 ± 2.9, and 16.0 ± 3.3, respectively. No significant difference was found between the IOP without and with manual UEE (IOP difference; all, P > .50; paired t test). Multiple linear regression analyses revealed that palpebral fissure height did not affect IOP difference for any of the tonometers. CONCLUSIONS: Simple manual UEE when measuring the IOP has little effect on the IOP obtained using all current rebound tonometers and GAT.

Novel predator-induced phenotypic plasticity by hemoglobin and physiological changes in the brain of Xenopus tropicalis.

Organisms adapt to changes in their environment to survive. The emergence of predators is an example of environmental change, and organisms try to change their external phenotypic systems and physiological mechanisms to adapt to such changes. In general, prey exhibit different phenotypes to predators owing to historically long-term prey-predator interactions. However, when presented with a novel predator, the extent and rate of phenotypic plasticity in prey are largely unknown. Therefore, exploring the physiological adaptive response of organisms to novel predators is a crucial topic in physiology and evolutionary biology. Counterintuitively, Xenopus tropicalis tadpoles do not exhibit distinct external phenotypes when exposed to new predation threats. Accordingly, we examined the brains of X. tropicalis tadpoles to understand their response to novel predation pressure in the absence of apparent external morphological adaptations. Principal component analysis of fifteen external morphological parameters showed that each external morphological site varied nonlinearly with predator exposure time. However, the overall percentage change in principal components during the predation threat (24 h) was shown to significantly (p < 0.05) alter tadpole morphology compared with that during control or 5-day out treatment (5 days of exposure to predation followed by 5 days of no exposure). However, the adaptive strategy of the altered sites was unknown because the changes were not specific to a particular site but were rather nonlinear in various sites. Therefore, RNA-seq, metabolomic, Ingenuity Pathway Analysis, and Kyoto Encyclopedia of Genes and Genomes analyses were performed on the entire brain to investigate physiological changes in the brain, finding that glycolysis-driven ATP production was enhanced and ß-oxidation and the tricarboxylic acid cycle were downregulated in response to predation stress. Superoxide dismutase was upregulated after 6 h of exposure to new predation pressure, and radical production was reduced. Hemoglobin was also increased in the brain, forming oxyhemoglobin, which is known to scavenge hydroxyl radicals in the midbrain and hindbrain. These suggest that X. tropicalis tadpoles do not develop external morphological adaptations that are positively correlated with predation pressure, such as tail elongation, in response to novel predators; however, they improve their brain functionality when exposed to a novel predator.

The urinary lipid profile in cats with idiopathic cystitis.

Although feline idiopathic cystitis (FIC) distresses of many cats, its pathogenesis is unknown and the diagnosis is challenging. Polyunsaturated fatty acids (PUFAs) are metabolized into various lipid mediators. Lipid mediators such as prostaglandins (PGs) modulate inflammation and many of them are excreted into the urine. Thus, the investigation of the urinary lipid profile may reveal pathogenesis and help diagnosis of FIC. We collected urine samples from five FIC cats by spontaneous urination and analyzed 158 types of lipid mediators in urines using liquid chromatography-mass spectrometry. The urinary levels of PUFAs were higher in FIC compared to those of the healthy group. The excretions of a major inflammatory mediator, PGD2, were less in FIC. Other well-known inflammatory mediators such as PGE2, PGI2, and their metabolites did not show a difference. In contrast, the levels of PGF2α and its 2 metabolites and PGF3α were higher in FIC. These results may provide new insights into the future management of cat FIC.

The profile of urinary lipid metabolites in cats with bacterial cystitis.

Bacterial cystitis is one of the feline lower urinary tract diseases (FLUTDs). Polyunsaturated fatty acids, such as arachidonic acid (ARA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA), are oxidized into various lipid mediators that modulate inflammation. Since the profile of lipid metabolites excreted in urine is useful for assessing inflammatory body conditions, we analyzed 126 types of urinary lipid metabolites in cats with bacterial cystitis. Using LC-MS/MS, we found that the levels of 11 metabolites were higher in the urine of cystitis cats than in the urine of healthy cats. In detail, the urinary levels of ARA, EPA, and DHA and eight of their metabolites were increased in cystitis cats. Focusing on the lipid oxidation pathway, the urinary levels of four cyclooxygenase-, three lipoxygenase-, and one cytochrome P450-dependent oxidated metabolites were increased in bacterial cystitis. These urinary lipid profiles can provide some insight into the pathology and future diagnosis of bacterial cystitis.

Equol-producing status affects exercise training-induced improvement in arterial compliance in postmenopausal women.

Central arterial compliance decreases drastically after menopause. Regular intake of soy isoflavone and aerobic exercise increase arterial compliance. The equol is a metabolite of isoflavone daidzein by gut microbiome. We determined whether the equol-producing status affects aerobic exercise-induced improvement in carotid arterial compliance. Forty-three postmenopausal women were assigned to two intervention groups: 1) exercise and isoflavone (Ex+Iso, n = 27 females) or 2) isoflavone interventions (Iso; n = 16 females). Participants of the Ex+Iso intervention group completed an 8-wk aerobic exercise training, and all participants were administered with oral isoflavone supplements during the interventions. The equol-producing status (equol producers or nonproducers) was determined from urine equol concentrations after a soy challenge. In the Ex+Iso intervention group, carotid arterial compliance increased in the equol producers (0.084 ± 0.030→0.117 ± 0.035 mm2/mmHg), but not in the nonproducers (0.089 ± 0.028→0.097 ± 0.026 mm2/mmHg) after the intervention (interaction effect; P < 0.05). The magnitude of increases in carotid arterial compliance was significantly greater in the equol producers than in the non-equol producers (P < 0.05). In the isoflavone intervention group, there were no changes in any parameters after the intervention irrespective of the equol status. These results suggest that equol-producing status is obligatory to aerobic exercise training-induced improvements in central arterial compliance in postmenopausal women.NEW & NOTEWORTHY Isoflavone intake and aerobic exercise increase central artery compliance. Equol, a metabolite of isoflavone daidzein by gut microbiome, has beneficial effects on vascular function. We demonstrated for the first time that the interaction of aerobic exercise and equol production status plays an essential role in improvements in central artery compliance in postmenopausal women. More specifically, the equol-producing status was obligatory to exercise training-induced improvements in central arterial compliance in postmenopausal women.

The profile of urinary lipid metabolites in cats.

Polyunsaturated fatty acids including arachidonic acid (AA), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), are converted to lipid mediators by oxidation. Unlike other mammals, cats cannot synthesize AA. Since their lipid metabolic features remain unknown, we qualitatively analyzed 118 types of urinary lipid metabolites in healthy neutered cats. Using LC-MS, we found 26 lipid metabolites in urines of all individuals. In detail, 20 AA-, 5 EPA- and 1 DHA-derived lipid mediators were detected. Focusing on oxidative pathway, 17 cyclooxygenase-metabolites and 5 metabolites produced by non-enzymatic pathway were detected. Of interest, few lipoxygenase- or cytochrome P450-metabolites were excreted. Thus, AA-derived cyclooxygenase-metabolites mainly composed the urinary lipid metabolites in cats.

Metabolic profiles of coumarin in human plasma extrapolated from a rat data set with a simplified physiologically based pharmacokinetic model.

Coumarin is a dietary-derived substance that is extensively metabolized by human liver to excretable 7-hydroxycoumarin. Although coumarin under daily dietary consumption is generally regarded as nontoxic, the substance is of toxicological and clinical interest because of its potential association with hepatotoxicity, which is especially evident in rats. In this study, the pharmacokinetics of coumarin were modeled after virtual oral administration in humans. The adjusted monitoring equivalents of coumarin, along with the biotransformation of coumarin to o-hydroxyphenylacetic acid (via 3,4-epoxidation) based on reported plasma concentrations from rat studies, were scaled to human coumarin equivalents using known species allometric scaling factors. Using rat and human liver preparations, data on the rapid in vitro metabolic clearance for humans (~50-fold faster than in rats) were obtained for in vitro-in vivo extrapolation. For human physiologically based pharmacokinetic (PBPK) modeling, the metabolic ratios to o-hydroxyphenylacetic acid and 7-hydroxycoumarin were set at minor (0.1) and major (0.9) levels for the total disappearance of coumarin. The resulting modeled plasma concentration curves in humans generated by simple PBPK models were consistent with reported simulated coumarin maximum concentrations. These results provide basic information to simulate plasma levels of coumarin and its primary metabolite 7-hydroxycoumarin or its secondary activated metabolite o-hydroxyphenylacetic acid (via 3,4-epoxidation) resulting from dietary foodstuff consumption. Under the current assumptions, little toxicological impact of coumarin was evident in humans, thereby indicating the usefulness of forward dosimetry using PBPK modeling for human risk assessment.

Time course of conjunctival hyperemia induced by omidenepag isopropyl ophthalmic solution 0.002%: a pilot, comparative study versus ripasudil 0.4.

OBJECTIVE: We investigated the detailed time course of conjunctival hyperemia induced by omidenepag isopropyl ophthalmic solution 0.002% (omidenepag), a selective prostaglandin E2 receptor 2 agonist. METHODS AND ANALYSIS: We recruited 34 healthy subjects and administered omidenepag in the right eye and ripasudil 0.4% in the left eye. We evaluated conjunctival hyperemia using slit-lamp photography at baseline and after 15, 30, 60, 120, 180 and 360 min. The conjunctival hyperemia score was graded by three independent observers using a scale from 0 (none) to 3 (severe). We also evaluated conjunctival hyperemia by the pixel coverage of conjunctival blood vessels (per cent coverage) determined using a conjunctival hyperemia-analysing software. RESULTS: In omidenepag, the conjunctival hyperemia score and per cent coverage peaked at both 30 min (mean score±SD: 1.57±0.67 and 11.90%±3.66%, respectively) and then gradually decreased at 60 min (10.79%±3.32%) and 120 min (1.10±0.52) when they reached a level that was not significantly different from the baseline values. For ripasudil 0.4%, the peak time of the conjunctival hyperemia score and per cent coverage were both at 15 min (score: 2.42±0.54 and 15.26%±3.38%). The degree of conjunctival hyperemia was significantly higher for ripasudil 0.4% than that for omidenepag from 15 to 30 min in both the conjunctival hyperemia score and per cent coverage (p<0.007 by Bonferroni correction). CONCLUSION: Conjunctival hyperemia induced by omidenepag gradually peaks to moderate severity, though weaker compared with that induced by ripasudil 0.4%, and subsides relatively quickly.

Genome-wide association study identifies CDH13 as a susceptibility gene for rhododendrol-induced leukoderma.

Racemic RS-4-(4-hydroxyphenyl)-2-butanol (rhododendrol; trade name: Rhododenol [RD]), which is used in topical skin-lightening cosmetics, was unexpectedly reported in Japan to induce leukoderma or vitiligo called RD-induced leukoderma (RIL) after repeated application. To our knowledge, no studies have investigated chemical-induced vitiligo pathogenesis on a genome-wide scale. Here, we conducted a genome-wide association study (GWAS) for 147 cases and 112 controls. CDH13, encoding a glycosylphosphatidylinositol-anchored protein called T-cadherin (T-cad), was identified as the strongest RIL susceptibility gene. RD sensitivity was remarkably increased by T-cad knockdown in cultured normal human melanocytes. Furthermore, we confirmed tyrosinase upregulation and downregulation of the anti-apoptotic molecules (BCL-2 and BCL-XL), suggesting that T-cad is associated with RD via tyrosinase or apoptotic pathway regulation. Finally, monobenzyl ether of hydroquinone sensitivity also tended to increase with T-cad knockdown, suggesting that the T-cad could be a candidate susceptibility gene for RIL and other chemical-induced vitiligo forms. This is the first GWAS for chemical-induced vitiligo, and it could be a useful model for studying the disease's genetic aspects.

The Molecular Basis of Chemical Chaperone Therapy for Oculocutaneous Albinism Type 1A.

Oculocutaneous albinism (OCA) is an autosomal recessive disease characterized by the reduction or complete lack of melanin pigment in the skin, hair, and eyes. No effective treatment for OCA is available at present. OCA type 1 is caused by mutations that disrupt the function of tyrosinase (TYR), the rate-limiting enzyme of melanin synthesis. Recently, it was shown that tyrosinase in some patients with OCA type 1 mutation is retained in the endoplasmic reticulum and that its catalytic activity is lost, a phenomenon known as endoplasmic reticulum retention. However, to our knowledge, the intracellular localization of tyrosinase in Japanese patients with OCA type 1 missense mutations has not been reported. In this study, we first investigated the intracellular localization of Japanese OCA type 1A missense mutant tyrosinases using Western blotting and immunohistochemical staining. R77Q, R239W, D383N, and P431L mutant tyrosinases were retained in the endoplasmic reticulum, and H211Y mutant tyrosinase was partially transported to the Golgi apparatus. Second, we explored the possibility of chemical chaperone therapy for Japanese patients with OCA type 1A missense mutations and found that HeLa cells expressing P431L mutant tyrosinase have restored tyrosinase activity after treatment with a low-dose tyrosinase inhibitor, as a chemical chaperone, in a dose-dependent manner. These results provide the basis for a possible chemical chaperone therapy to recover tyrosinase activities in patients with OCA type 1A patients.

Comparison of the Intraocular Pressure Measured Using the New Rebound Tonometer Icare ic100 and Icare TA01i or Goldmann Applanation Tonometer.

PURPOSE: We evaluated the agreement between the intraocular pressure (IOP) values of new rebound tonometer, Icare ic100, and Icare TA01i or Goldmann applanation tonometer (GAT). METHODS: We studied one eye each of 106 subjects (57 with primary open-angle glaucoma, 49 healthy subjects). IOP was randomly measured twice with the patient in sitting position using the Icare ic100, Icare TA01i, and GAT. Tonometer measurements were evaluated using Bland-Altman analysis. The relationship between IOP difference (Icare ic100-GAT) and age, sex, disease, axial length, central corneal thickness (CCT), and corneal curvature was investigated using multivariate regression analysis. RESULTS: IOPs measured using Icare ic100, Icare TA01i, and GAT were 11.7±3.0 (mean±standard deviation), 12.2±2.9, and 16.0±3.2 mm Hg, respectively (P<0.001, one-way analysis of variance). Icare ic100 showed significantly lower IOPs than GAT (P<0.05), but not than Icare TA01 (P>0.05; Tukey-Kramer test). Bland-Altman analysis revealed that the mean differences between Icare ic100 and Icare TA01i and those between Icare ic100 and GAT were -0.46 and -4.2 mm Hg, respectively (95% limits of agreement, -3.35 to 2.42 and -10.10 to 1.61 mm Hg, respectively). For IOP differences between Icare ic100 and GAT, parameters selected in the optimal model were CCT (coefficient, 20.3, P=0.029), corneal curvature (3.0, P=0.020), and glaucoma-normal (-1.0, P=0.004). CONCLUSIONS: The new rebound tonometer Icare ic100 almost constantly showed IOPs lower than GAT. The difference was affected by CCT, corneal curvature, and disease.

Iris Thickness and Severity of Neovascular Glaucoma Determined Using Swept-Source Anterior-segment Optical Coherence Tomography.

PURPOSE: To investigate the iris thickness (IT) in neovascular glaucoma (NVG) using swept-source anterior-segment optical coherence tomography (ASOCT). PATIENTS AND METHODS: In this retrospective, clinic-based, comparative study, we enrolled 20 NVG patients [11 with 360-degree angle-closure (AC)-NVG and 9 with NVG without AC] and 14 healthy age-matched controls. Horizontal scanning images of swept-source ASOCT were analyzed using software calipers in temporal and nasal angle areas. ITs at 1 and 2 mm from the pupil edge were measured using ASOCT. The relation between IT and the severity of NVG, the effects of intraocular pressure (IOP), intravitreal antivascular endothelial growth factor (anti-VEGF) injection, and panretinal photocoagulation (PRP) were assessed using linear regression analysis based on the corrected Akaike information criteria index. RESULTS: The IT was thinner in 360-degree AC-NVG patients, followed by NVG patients without AC and controls (0.33 vs. 0.48 vs. 0.57 mm at 1 mm and 0.31 vs. 0.43 vs. 0.49 mm at 2 mm; P<0.001 by ANOVA). Multiple linear regression analysis revealed that 360-degree AC-NVG patients-NVG patients without AC and controls (coefficient: -0.16), NVG patients without AC-control (-0.13) and underwent PRP (0.23) at 1 mm, 360-degree AC-NVG patients-NVG patients without AC and controls (-0.12), NVG patients without AC-controls (-0.08), underwent PRP (0.16), received anti-VEGF injection (0.05) and IOP (-0.001) at 2 mm were selected predictors to explain IT. CONCLUSIONS: IT decreases with the progression of the NVG stage and is thinnest in 360-degree AC-NVG patients. Our study suggests a new morphologic feature of NVG.

Iris Morphological Features in Patients with 360° Angle-Closure Neovascular Glaucoma: An Anterior Segment Optical Coherence Tomography Study.

PURPOSE: To investigate iris morphological features in 360° angle-closure neovascular glaucoma (NVG) by swept-source anterior segment optical coherence tomography (ASOCT). PATIENTS AND METHODS: In this retrospective, clinic-based, comparative study, 14 patients with 360° angle-closure NVG and 14 healthy age-matched control subjects were enrolled. All patients enrolled had no prior glaucoma surgery but underwent cataract surgery with intraocular lens implantation. Horizontal scanning images of swept-source ASOCT were analyzed using software calipers in temporal and nasal angle areas. The iris thickness at 1 and 2 mm from the pupil edge, iris length, trabecular meshwork length, peripheral anterior synechia (PAS) length, PAS height ratio (PAS length/trabecular meshwork length), and pupil diameter were measured. RESULTS: Between the groups, there were no statistically significant differences in iris length, trabecular meshwork length, and pupil diameter (p > 0.05). However, the iris thickness was significantly reduced in the NVG group compared with the control group in the temporal and nasal areas (0.306 vs. 0.563 mm/0.326 vs. 0.645 mm at 1 mm, 0.278 vs. 0.523 mm/0.282 vs. 0.546 mm at 2 mm, respectively) (mean, all p < 0.001). In the NVG group, PAS height ratios were 1.55 ± 0.45 (mean ± standard deviation) (range, 0.58-2.30) and 1.55 ± 0.78 (range, 0.68-3.68) at the temporal and nasal angles, respectively. CONCLUSIONS: In patients with 360° angle-closure NVG, the iris thickness decreased to about 50% of that in healthy subjects, and the PAS length exceeded the trabecular meshwork length by about 1.5 times.