Population-based and interventional studies have shown that elevated zinc levels can reduce the progression to advanced age-related macular degeneration. The objective of this study was to assess whether elevated extracellular zinc has a direct effect on retinal pigment epithelial cells (RPE), by examining the phenotype and molecular characteristics of increased extracellular zinc on human primary RPE cells. Monolayers of human foetal primary RPE cells were grown on culture inserts and maintained in medium supplemented with increasing total concentrations of zinc (0, 75, 100, 125 and 150 μM) for up to 4 weeks. Changes in cell viability and differentiation as well as expression and secretion of proteins were investigated. RPE cells developed a confluent monolayer with cobblestone morphology and transepithelial resistance (TER) >200 Ω*cm within 4 weeks. There was a zinc concentration-dependent increase in TER and pigmentation, with the largest effects being achieved by the addition of 125 μM zinc to the culture medium, corresponding to 3.4 nM available (free) zinc levels. The cells responded to addition of zinc by significantly increasing the expression of Retinoid Isomerohydrolase (RPE65) gene; cell pigmentation; Premelanosome Protein (PMEL17) immunoreactivity; and secretion of proteins including Apolipoprotein E (APOE), Complement Factor H (CFH), and High-Temperature Requirement A Serine Peptidase 1 (HTRA1) without an effect on cell viability. This study shows that elevated extracellular zinc levels have a significant and direct effect on differentiation and function of the RPE cells in culture, which may explain, at least in part, the positive effects seen in clinical settings. The results also highlight that determining and controlling of available, as opposed to total added, zinc will be essential to be able to compare results obtained in different laboratories.
The phenomenon of contrasting color perceptions of "the dress" photograph has gained scientific interest. The mechanism underlying why individuals differ is yet to be fully explained. We use the powerful twin model design to ascertain the relative contribution of genetic and environmental factors on perception variation. A sample of 466 twins from the British TwinsUK registry were invited to report what color they saw in a standard image of the dress in standard illumination. The mean age of the participants was 49.5 (SD = 17.8) years, and 85% were female. When asked to choose between white and gold (WG) or blue and black (BB), 328 reported WG (70.4%) and 135 (29.0%) reported BB. Subjects choosing WG were significantly older (p < 0.01), but there was no significant difference in gender. Monozygotic (MZ) twins were more concordant in their responses than dizygotic (DZ) twins (0.46 vs. 0.36). Twin modeling revealed that genetic factors accounted for 34% (95% confidence interval, 5%-59%) of variation in the reported color of the dress when adjusted for age, whereas environmental factors contributed 66% (95% CI, 41%-95%). This study suggests environmental factors play a significant role in how an individual perceives the color of "the dress."
Significance
Myopia prevalence has increased dramatically over recent decades. Genome-wide association studies have identified numerous loci, but mechanisms by which genotypic identity confers myopia susceptibility are unknown. The common variant most strongly associated with myopia is near a gene encoding retinal gap junctions. We analyzed retinal electrophysiological responses from 186 twins genotyped at this locus, finding association between cone-driven, but not rod-driven, electroretinogram signals and allelic genotype. Examination of responses to further, nonstandard testing protocols, together with recordings from patients with selective loss of bipolar cell signals, points to an effect on cone-driven hyperpolarizing (“OFF”) signals. The pattern of retinal expression of this gene appears consistent with these findings, which support a potential role for altered cone-driven signaling in myopia development.
We herein present the case of a 15-month-old with visceral leishmaniasis diagnosed in the UK following a short trip to a popular holiday destination in Spain. Four months after the initial symptoms, the diagnosis was made incidentally on microscopy of a bone marrow biopsy taken for suspected haematological malignancy after the child developed hepatosplenomegaly, pancytopaenia, and Klebsiella pneumoniae septicaemia.
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