Diagnostic assessment of glaucoma and non-glaucomatous optic neuropathies via optical texture analysis of the retinal nerve fibre layer

The clinical diagnostic evaluation of optic neuropathies relies on the analysis of the thickness of the retinal nerve fibre layer (RNFL) by optical coherence tomography (OCT). However, false positives and false negatives in the detection of RNFL abnormalities are common. Here we show that an algorithm integrating measurements of RNFL thickness and reflectance from standard wide-field OCT scans can be used to uncover the trajectories and optical texture of individual axonal fibre bundles in the retina and to discern distinctive patterns of loss of axonal fibre bundles in glaucoma, compressive optic neuropathy, optic neuritis and non-arteritic anterior ischaemic optic neuropathy. Such optical texture analysis can detect focal RNFL defects in early optic neuropathy, as well as residual axonal fibre bundles in end-stage optic neuropathy that were indiscernible by conventional OCT analysis and by red-free RNFL photography. In a diagnostic-performance study, optical texture analysis of the RNFL outperformed conventional OCT in the detection of glaucoma, as defined by visual-field testing or red-free photography. Our findings show that optical texture analysis of the RNFL for the detection of optic neuropathies is highly sensitive and specific

Hyperglycemia impedes definitive endoderm differentiation of human embryonic stem cells by modulating histone methylation patterns

Exposure to maternal diabetes during fetal growth is a risk factor for the development of type II diabetes (T2D) in later life. Discovery of the mechanisms involved in this association should provide valuable background for therapeutic treatments. Early embryogenesis involves epigenetic changes including histone modifications. The bivalent histone methylation marks H3K4me3 and H3K27me3 are important for regulating key developmental genes during early fetal pancreas specification. We hypothesized that maternal hyperglycemia disrupted early pancreas development through changes in histone bivalency. A human embryonic stem cell line (VAL3) was used as the cell model for studying the effects of hyperglycemia upon differentiation into definitive endoderm (DE), an early stage of the pancreatic lineage. Hyperglycemic conditions significantly down-regulated the expression levels of DE markers SOX17, FOXA2, CXCR4 and EOMES during differentiation. This was associated with retention of the repressive histone methylation mark H3K27me3 on their promoters under hyperglycemic conditions. The disruption of histone methylation patterns was observed as early as the mesendoderm stage, with Wnt/β-catenin signaling being suppressed during hyperglycemia. Treatment with Wnt/β-catenin signaling activator CHIR-99021 restored the expression levels and chromatin methylation status of DE markers, even in a hyperglycemic environment. The disruption of DE development was also found in mouse embryos at day 7.5 post coitum from diabetic mothers. Furthermore, disruption of DE differentiation in VAL3 cells led to subsequent impairment in pancreatic progenitor formation. Thus, early exposure to hyperglycemic conditions hinders DE development with a possible relationship to the later impairment of pancreas specification

Fertility study of complement-3 in mice

Session: SRB Orals - Embryo DevelopmentHuman oviductal cells produce complement-3 (C3) and its embryotrophic derivative, iC3b in the presence of embryos. We proposed that C3-deficiency would lead to fertility impairment in mice in vivo. To determine the physiological significance of this protein in reproduction, heterozygous mice carrying the mutated C3 gene (C57BL/6J-C3tmlCrr) were purchased from Jackson Laboratory. Crossing of these mice (C3+/-) generated mice carrying the homozygous (C3+/+) and mutated C3 (C3-/-) genes. C3-/- and the wild type C3+/+ were allowed to cage with males of the same genotype for 6 months and their fertility was examined. Both genotypes are fertile and produce viable pups. The number of litters per week born from C3-/- pairs (0.116±0.05) were significantly smaller than those in C3 +/+ pairs (0.168±0.04). There were no significant difference between the mean numbers of pups per litter, mean born weight and mean litter size at wean between the two groups. However, the mean pup weight at weaning of C3 -/- pairs (8.1± 1.2 g .) was significantly smaller than that of C3 +/+ pairs (8.6±1.3 g). Although C3 protein could not be detected in the C3 -/- mice serum by Western blot, C3 immunoreactivity and mRNA was detected in the oviduct and liver tissues homogenate, suggesting the presence of mutated C3 molecules in these animals. These mating results suggested that the C3 -/- mice require longer getting pregnant and the resulting pups are smaller in size at weaning. The biological activity of the mutated C3 molecule on embryo development remains to be investigated

Dynamic analysis of dark-light changes of the anterior chamber angle with anterior segment OCT

PURPOSE. To describe the use of anterior segment optical coherence tomography (OCT) in studying the dynamic dark-light changes of the anterior chamber angle. METHODS. Thirty-seven normal subjects with open angles on dark-room gonioscopy and 18 subjects with narrow angles were analyzed. The dynamic dark-light changes of the anterior-chamber angle were captured with real-time video recording. The angle opening distance (AOD500) and trabecular iris space area (TISA500) of the nasal angle and the pupil diameter in each of the representative serial images were measured. Linear regression analysis was performed to investigate the association between AOD500/TISA500 and pupil diameter. Demographic and biometry measurements associated with the AOD difference (AOD500 (light) - AOD500 (dark)) and TISA difference (TISA500 (light) - TISA500 (dark)) were analyzed with univariate and multivariate regression models. RESULTS. The AOD500/TLSA500 measured in the light in the open-angle and the narrow-angle groups were 694 ± 330 μm/0.24 ± 0.10 mm 2 and 265 ±78 μm/0.10 ± 0.03 mm 2, respectively. These values were significantly greater than the AOD500/TISA500 measured in the dark (492 ± 265 μm/0.16 ± 0.08 mm 2 and 119 ± 82 μm/0.05 ± 0.04 mm 2, respectively, all with P < 0.001). The ranges of the AOD/TISA difference were 13 to 817 μm/0.011 to 0.154 mm 2, with an average of 180 μm/0.073 mm 2. Multivariate regression analysis identified a positive correlation between anterior chamber depth and the AOD/TISA difference. Fifty eyes showed significant correlations between AOD/TISA and pupil diameter, whereas one eye showed no association. Four eyes in the narrow angle group developed appositional angle closure in the dark. CONCLUSIONS. The dynamic dark-light changes of the anterior chamber angle can be imaged and analyzed with anterior segment OCT. Although the angle width generally decreased linearly with increasing pupil diameter, the differences of the angle width measured in the dark and in the light varied substantially among individuals. Copyright © Association for Research in Vision and Ophthalmology.link_to_subscribed_fulltex

A phase 2 study of neoadjuvant chemotherapy using combined taxane, anthracycline, and cyclophosphamide in high risk HER2-negative locally advanced breast cancer

Oral Presentatio

Microvascular network alterations in the retina of patients with Alzheimer's disease

Background: Although cerebral small-vessel disease has been implicated in the development of Alzheimer's disease (AD), the cerebral microcirculation is difficult to visualize directly in vivo. Because the retina provides a noninvasive window to assess the microcirculation, we determined whether quantitatively measured retinal microvascular parameters are associated with AD. Methods: We conducted a case-control study (case:control matching approximate to 1:2). Retinal photographs were analyzed using a computer program, and a spectrum of quantitative retinal microvascular parameters (caliber, fractal dimension, tortuosity, and bifurcation) were measured. Logistic regression models were used to compute the odds ratio (OR) and 95% confidence interval for AD adjusting for age, gender, ethnicity, smoking, hypertension, diabetes, hypercholesterolemia, and history of myocardial infarction. Results: We included 136 demented patients with AD and 290 age-gender-race-matched controls. Persons with narrower venular caliber (OR per standard deviation [SD] decrease, 2.01 [1.27-3.19]), decreased arteriolar and venular fractal dimension (OR per SD decrease 1.35 [1.08-1.68], 1.47 [1.17-1.84], respectively) and increased arteriolar and venular tortuosity (OR per SD increase, 1.84 [1.40-2.31], 1.94 [1.48-2.53], respectively) were more likely to have AD. These associations still persisted when only AD cases without a history of cerebrovascular disease were included. Conclusions: Patients with AD have altered microvascular network in the retina (narrower retinal venules and a sparser and more tortuous retinal vessels) compared with matched nondemented controls. These changes in retinal microvasculature may reflect similar pathophysiological processes in cerebral microvasculature in the brains of patients with AD. (C) 2014 The Alzheimer's Association. All rights reserved