Predicting Vision Loss In Healthy Aging With Manganese-Enhanced Mri Of The Rat Eye

In healthy aging, visual function declines throughout adulthood. Age-related changes in neuronal ion homeostasis -- specifically, increased Ca2+ influx through L-type voltage gated calcium channels (L-VGCCs) -- are believed to contribute to certain functional declines, but this possibility has not yet been tested in the neural retina. In young, mid- and old adult Long-Evans rats, we compared visual function (optokinetic tracking), as well as retinal physiology and eye morphology (Mn2+-enhanced MRI (MEMRI), which uses neuronal Mn2+ uptake as a marker of Ca2+ influx). We documented significant age-related decreases in visual performance and increases in retinal ion influx. We confirmed that Mn2+ uptake was regulated by L-VGCC using systemic and topical application of the L-VGCC antagonist nifedipine, and discovered an age-related change in sensitivity to L-VGCC blocker diltiazem. Based on Western blot studies, we find this sensitivity change to be consistent with the age-dependant appearance of drug-insensitive L-VGCC isoforms. Longitudinally, rats starting the study with relatively high retinal Mn2+ uptake, compared to other cohort members, experienced significantly greater declines in contrast sensitivity in the ~4.5 mo following MRI. Independent of that relationship, rats starting the study with relatively large eyes experienced significantly greater declines in contrast sensitivity. The latter finding suggests that particularly rapid juvenile or young-adult growth is a risk factor for particularly rapid senescence. Longitudinally, we found no evidence of retinal volume loss, and found that changes in retinal volume were not correlated with changes in visual function -- suggesting that age-related vision declines cannot be explained by neuron loss. In summary, our longitudinal studies identify two previously-unknown risk factors for age-related vision declines: rapid eye growth in early life, and age-related changes in L-VGCC-dependent retinal ion physiology

Carbogaseous spring waters, coldwater geysers and dry CO2 exhalations in the tectonic window of the Lower Engadine Valley, Switzerland

Abstract.: In the region of Scuol-Tarasp in the Lower Engadine Valley in the Eastern Swiss Alps, there are a variety of phenomena related to a geogenetic CO2 production, including carbogaseous mineral springs, previously active coldwater geysers and dry gas exhalations from the ground via mofettes. Previous isotopic studies revealed that the CO2 originates from the metamorphic decomposition of carbonate rocks in the crust. This paper presents an inventory of the springs, geysers and mofettes, and proposes a conceptual model on the regional gas and water circulation. Based on hydrochemical criteria, it was possible to identify six main groups of spring waters, three of which are carbogaseous mineral springs. Most of the carbogaseous springs and gas exhalations are bound to the Bündnerschiefer fractured aquifer. The different water types originate from mixing of groundwater and highly mineralised carbogaseous fluids from depth. Near-surface degassing of CO2 from the fluid phase creates the dry gas exhalations. CO2 and radon measurements in 178 soil boreholes suggest that the gas exhalations occur at a limited number of point-like anomalies, and there is no evidence for regionally important diffuse CO2 discharges from the groun

Refractive Development in the “ROP Rat”

Although retinopathy of prematurity (ROP) is clinically characterized by abnormal retinal vessels at the posterior pole of the eye, it is also commonly characterized by vascular abnormalities in the anterior segment, visual dysfunction which is based in retinal dysfunction, and, most commonly of all, arrested eye growth and high refractive error, particularly (and paradoxically) myopia. The oxygen-induced retinopathy rat model of ROP presents neurovascular outcomes similar to the human disease, although it is not yet known if the “ROP rat” also models the small-eyed myopia characteristic of ROP. In this study, magnetic resonance images (MRIs) of albino (Sprague-Dawley) and pigmented (Long-Evans) ROP rat eyes, and age- and strain-matched room-air-reared (RAR) controls, were examined. The positions and curvatures of the various optical media were measured and the refractive state (℞) of each eye estimated based on a previously published model. Even in adulthood (postnatal day 50), Sprague-Dawley and Long-Evans ROP rats were significantly myopic compared to strain-matched controls. The myopia in the Long-Evans ROP rats was more severe than in the Sprague-Dawley ROP rats, which also had significantly shorter axial lengths. These data reveal the ROP rat to be a novel and potentially informative approach to investigating physiological mechanisms in myopia in general and the myopia peculiar to ROP in particular

Systemic Retinaldehyde Treatment Corrects Retinal Oxidative Stress, Rod Dysfunction, and Impaired Visual Performance in Diabetic MiceSystemic Retinaldehyde Treatment in Diabetic Mice

PurposeDiabetes appears to induce a visual cycle defect because rod dysfunction is correctable with systemic treatment of the visual cycle chromophore 11-cis-retinaldehyde. However, later studies have found no evidence for visual cycle impairment. Here, we further examined whether photoreceptor dysfunction is corrected with 11-cis-retinaldehyde. Because antioxidants correct photoreceptor dysfunction in diabetes, the hypothesis that exogenous visual chromophores have antioxidant activity in the retina of diabetic mice in vivo was tested.MethodsRod function in 2-month-old diabetic mice was evaluated using transretinal electrophysiology in excised retinas and apparent diffusion coefficient (ADC) MRI to measure light-evoked expansion of subretinal space (SRS) in vivo. Optokinetic tracking was used to evaluate cone-based visual performance. Retinal production of superoxide free radicals, generated mostly in rod cells, was biochemically measured with lucigenin. Diabetic mice were systemically treated with a single injection of either 11-cis-retinaldehyde, 9-cis-retinaldehyde (a chromophore surrogate), or all-trans-retinaldehyde (the photoisomerization product of 11-cis-retinaldehyde).ResultsConsistent with previous reports, diabetes significantly reduced (1) dark-adapted rod photo responses (transretinal recording) by ∼18%, (2) rod-dominated light-stimulated SRS expansion (ADC MRI) by ∼21%, and (3) cone-dominated contrast sensitivity (using optokinetic tracking [OKT]) by ∼30%. Both 11-cis-retinaldehyde and 9-cis-retinaldehyde largely corrected these metrics of photoreceptor dysfunction. Higher-than-normal retinal superoxide production in diabetes by ∼55% was also significantly corrected following treatment with 11-cis-retinaldehyde, 9-cis-retinaldehyde, or all-trans-retinaldehyde.ConclusionsCollectively, data suggest that retinaldehydes improve photoreceptor dysfunction in diabetic mice, independent of the visual cycle, via an antioxidant mechanism

Swiss Marketing Leadership Studie 2016 : digitale Transformation im Marketing

Die meisten Schweizer Unternehmen haben verstanden, dass die Digitale Transformation das Marketing grundlegend verändert. Doch vielerorts fehlt es an strategischer Verankerung, Systematik und Ressourcen. Das Institut für Marketing Management der ZHAW School of Management hat am 8. September im Rahmen des Swiss CRM Forum seine diesjährige Swiss Marketing Leadership Studie vorgestellt. Die Befragung von 646 Schweizer Unternehmen zeigt, dass hierzulande ein grundlegendes Verständnis für die Veränderungen im Marketing vorhanden ist, welche die Digitale Transformation mit sich bringt. Allerdings befinden sich viele Unternehmen noch am Anfang des Transformationsprozesses. Auch nicht alle Unternehmen sehen die Entwicklung vornehmlich als Chance. Bisweilen fürchtet man eine Bedrohung des Status quo. Insgesamt zeigt sich, dass hierzulande noch viele Herausforderungen zu meistern sind, will man weiterhin im internationalen Wettbewerb mithalten können.­­ Kundenbeziehungsmanagement als Treiber: Bei B2C-Unternehmen geniesst die Digitale Transformation einen signifikant höheren Stellenwert als im B2B-Bereich. Insbesondere das Kundenbeziehungsmanagement gilt vielerorts als Katalysator der Entwicklung. Weniger ausgeprägt ist das Verständnis für den Wandel hingegen im Produktmanagement, wo entsprechende Methoden und Tools noch eine untergeordnete Rolle spielen. Zudem zeigt sich, dass kaum ein Unternehmen bisher ein ganzheitliches, toolbasiertes Product-Lifecycle-Management betreibt. Fachleute verzweifelt gesucht: Gemäss Studie planen Schweizer Unternehmen mehr denn je, in das Kundenbeziehungsmanagement zu investieren. Allerdings zeigen sich dabei grosse Unterschiede: Je reifer das Unternehmen bezüglich Digitalisierung, desto grösser die Bereitschaft für Investitionen. Ausserdem gibt es grosse branchenspezifische Unterschiede. Trotz teilweise reger Aktivität fehlt es jedoch an strategischer Verankerung, Systematik und vor allem Ressourcen. Entsprechende Budgets sind zwar vielerorts vorhanden, doch die Rekrutierung geeigneter Mitarbeitenden stellt eine grosse Herausforderung dar. Die Studie wurde in Zusammenarbeit mit zahlreichen Partnern aus der Privatwirtschaft realisiert

Unexpected spatial distribution of bubble rearrangements in coarsening foams

Foams are ideal model systems to study stress-driven dynamics, as stress-imbalances within the system are continuously generated by the coarsening process, which unlike thermal fluctuations, can be conveniently quantified by optical means. However, the high turbidity of foams generally hinders the detailed study of the temporal and spatial distribution of rearrangement events, such that definite assessments regarding their contribution to the overall dynamics could not be made so far. In this paper, we use novel light scattering techniques to measure the frequency and position of events within a large sample volume. As recently reported (A. S. Gittings and D. J. Durian, Phys. Rev. E, 2008, 78, 066313), we find that the foam dynamics is determined by two distinct processes: intermittent bubble rearrangements of finite duration and a spatially homogeneous quasicontinuous process. Our experiments show that the convolution of these two processes determines the age-dependence of the mean dynamics, such that relations between intermittent rearrangements and coarsening process can not be established by considering means. By contrast the use of the recently introduced photon correlation imaging technique (A. Duri, D. A. Sessoms, V. Trappe, and L. Cipelletti, Phys. Rev. Lett., 2009, 102, 085702) enables us to assess that the event frequency is directly determined by the strain-rate imposed by the coarsening process. Surprisingly, we also find that, although the distribution of successive events in time is consistent with a random process, the spatial distribution of successive events is not random: rearrangements are more likely to occur within a recently rearranged zone. This implies that a topological rearrangement is likely to lead to an unstable configuration, such that a small amount of coarsening-induced strain is sufficient to trigger another event