Electrical responses from human retinal cone pathways associate with a common genetic polymorphism implicated in myopia.

Myopia is the commonest visual impairment. Several genetic loci confer risk, but mechanisms by which they do this are unknown. Retinal signals drive eye growth, and myopia usually results from an excessively long eye. The common variant most strongly associated with myopia is near the GJD2 gene, encoding connexin-36, which forms retinal gap junctions. Light-evoked responses of retinal neurons can be recorded noninvasively as the electroretinogram (ERG). We analyzed these responses from 186 adult twin volunteers who had been genotyped at this locus. Participants underwent detailed ERG recordings incorporating international standard stimuli as well as experimental protocols aiming to separate dark-adapted rod- and cone-driven responses. A mixed linear model was used to explore association between allelic dosage at the locus and international standard ERG parameters after adjustment for age, sex, and family structure. Significant associations were found for parameters of light-adapted, but not dark-adapted, responses. Further investigation of isolated rod- and cone-driven ERGs confirmed associations with cone-driven, but not rod-driven, a-wave amplitudes. Comparison with responses to similar experimental stimuli from a patient with a prior central retinal artery occlusion, and from two patients with selective loss of ON-bipolar cell signals, was consistent with the associated parameters being derived from signals from cone-driven OFF-bipolar cells. Analysis of single-cell transcriptome data revealed strongest GJD2 expression in cone photoreceptors; bipolar cell expression appeared strongest in OFF-bipolar cells and weakest in rod-driven ON-bipolar cells. Our findings support a potential role for altered signaling in cone-driven OFF pathways in myopia development.

Do twins share the same dress code? Quantifying relative genetic and environmental contributions to subjective perceptions of "the dress" in a classical twin study.

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."

IDENTIFICATION OF INCREASED BLUE LIGHT REFLECTIVITY IN MACULAR TELANGIECTASIA TYPE 2 USING SCANNING LASER OPHTHALMOSCOPY VERSUS RED-FREE FUNDUS PHOTOGRAPHY.

PURPOSE: To compare two modalities used for detection of the characteristic parafoveal hyperreflective area seen in macular telangiectasia Type 2. METHODS: Scanning laser ophthalmoscope blue light reflectance was compared with red-free fundus photography imaging. Images were obtained as part of the international Natural History Study of Macular Telangiectasia (MacTel Study). RESULTS: The hyperreflective area can more frequently be seen with scanning laser ophthalmoscope blue light reflectance than with red-free imaging. CONCLUSION: Detection of the hyperreflective area might help to identify macular telangiectasia in earlier disease stages. Scanning laser ophthalmoscope blue light reflectance should be preferred as a diagnostic tool when the suspicion of macular telangiectasia arises. However, red-free imaging offers a viable option to scanning laser ophthalmoscope blue light reflectance when good quality is achieved.

Charles Bonnet syndrome and periodic alternating nystagmus: Moving visual hallucinations.

OBJECTIVE: To describe and discuss potential mechanisms for modulation of visual hallucinations by nystagmus. METHODS: We present 2 patients with coexistent Charles Bonnet syndrome and periodic alternating nystagmus in the context of acquired visual loss. RESULTS: The combination has given rise to a rare phenomenon: visual hallucinations that move in a manner governed by the nystagmus, specifically by the direction and velocity of the slow phase. The perceived modulation of movement is selective for a surface in one case and a landscape in the other but not present for hallucinated individual objects and people separate from the hallucinated background visual scene. CONCLUSIONS: The collision of Charles Bonnet syndrome and periodic alternating nystagmus in these 2 patients has demonstrated that some visual hallucinations can be modulated by, or collaterally with, ocular movements. We propose 2 potential mechanisms based on ocular proprioceptive input from extraocular muscles projecting to either extrastriate processing of visual scene, or to higher-order visual cortical areas involved in analysis of motion signals across the whole visual field.

The effects of zinc supplementation on primary human retinal pigment epithelium.

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*cm2 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.

Visceral Leishmaniasis in a UK Toddler following a Short Trip to a Popular Holiday Destination in Spain.

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.