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The data show that the centripetal displacement of the inner foveal layers in eyes with macular pucker, which results in a disappearance of the foveal pit, may also generate foveal herniation which is suggested to be caused by contraction of Müller cell processes in the OPL. The centripetal displacement of the inner foveal layers and the formation of foveal herniation are suggested to reverse the foveal pit formation during development.Neuronal ceroid lipofuscinoses (NCL; Batten disease) are a group of inherited neurodegenerative diseases primarily affecting children. A common feature across most NCLs is the progressive loss of vision. We performed intravitreal injections of self-complementary AAV9 vectors packaged with either ovine CLN5 or CLN6 into one eye of 3-month-old CLN5-/- or CLN6-/- animals, respectively. Electroretinography (ERG) was performed every month following treatment, and retinal histology was assessed post-mortem in the treated compared to untreated eye. In CLN5-/- animals, ERG amplitudes were normalised in the treated eye whilst the untreated eye declined in a similar manner to CLN5 affected controls. In CLN6-/- animals, ERG amplitudes in both eyes declined over time although the treated eye showed a slower decline. Post-mortem examination revealed significant attenuation of retinal atrophy and lysosomal storage body accumulation in the treated eye compared with the untreated eye in CLN5-/- animals. This proof-of-concept study provides the first observation of efficacious intravitreal gene therapy in a large animal model of NCL. In particular, the single administration of AAV9-mediated intravitreal gene therapy can successfully ameliorate retinal deficits in CLN5-/- sheep. Combining ocular gene therapy with brain-directed therapy presents a promising treatment strategy to be used in future sheep trials aiming to halt neurological and retinal disease in CLN5 Batten disease.In broadband light, longitudinal chromatic aberration (LCA) provides emmetropization signals from both wavelength defocus and the resulting chromatic cues. Indoor illuminants vary in their spectral output, potentially limiting the signals from LCA. Our aim is to investigate the effect that artificial illuminants with different spectral outputs have on chick emmetropization with and without low temporal frequency modulation. In Experiment 1, two-week-old chicks were exposed to 0.2 Hz, square-wave luminance modulation for 3 days. There were 4 spectral conditions LED strips that simulated General Electric (GE) LED “Soft” (n = 13), GE LED “Daylight” (n = 12), a novel “Equal” condition (n = 12), and a novel “High S” condition (n = 10). These conditions were all tested at a mean level of 985 lux. In Experiment 2, the effect of intensity on the “Equal” condition was tested at two other light levels (70 lux n = 10; 680 lux n = 7). In Experiment 3, the effect of temporal modulation on the “Equal” condition was tested by comparing the 0.2 Hz condition with 0 Hz (steady). Significant differences were found in axial growth across lighting conditions. At 985 lux, birds exposed to the “Equal” condition showed a greater reduction in axial growth (both p less then 0.01) and a greater hyperopic shift compared to “Soft” and “Daylight” (both p less then 0.01). The “High S” birds experienced more axial growth compared to “Equal” (p less then 0.01) but less than in “Soft” and “Daylight” (p less then 0.01). Axial changes in “Equal” were only observed at 985 lux with 0.2 Hz temporal modulation, and not with lower light levels or steady light. We conclude that axial growth and refraction were dependent on the lighting condition in a manner predicted by wavelength defocus signals arising from LCA.Most studies of the effect of acute elevation of intraocular pressure (IOP) on ocular blood-flow have utilized optical coherence tomography (OCT) to characterize retinal and choroidal flow and vascular density. This study investigates the effect of acute IOP elevation on blood flow velocity in the retrobulbar arteries and veins supplying and draining the eye, which, unlike the retinal and choroidal vasculature, are not directly compressed as IOP is increased. By cannulation of the anterior chamber of 20 Sprague-Dawley rats, we increased IOP in 10 mmHg steps from 10 to 60 mmHg and returned to 10 mmHg. After 1 min at each IOP (and 3 min after return to 10 mmHg), we acquired 18 MHz plane-wave ultrasound data at 3000 compound images/sec for 1.5 s. We produced color-flow Doppler images by digital signal processing of the ultrasound data, identified retrobulbar arteries and veins, generated spectrograms depicting flow velocity over the cardiac cycle and characterized changes of vascular density and perfusion in theen as volumetric venous outflow decreased at high IOP. The continued reduction in orbital vascular density 3 min after restoration of IOP to 10 mmHg might be attributable to persisting narrowing of capillaries, but this needs to be verified in future studies.Age-related macular degeneration (AMD) is the most common cause of central vision loss among elderly populations in industrialized countries. Genome-wide association studies have consistently associated two genomic loci with progression to late-stage AMD the complement factor H (CFH) locus on chromosome 1q31 and the age-related maculopathy susceptibility 2-HtrA serine peptidase 1 (ARMS2-HTRA1) locus on chromosome 10q26. While the CFH risk variant has been shown to alter complement activity, the ARMS2-HTRA1 risk haplotype remains enigmatic due to high linkage disequilibrium and inconsistent functional findings spanning two genes that are plausibly causative for AMD risk. In this review, we detail the genetic and functional evidence used to support either ARMS2 or HTRA1 as the causal gene for AMD risk, emphasizing both the historical development and the current understanding of the ARMS2-HTRA1 locus in AMD pathogenesis. Sitagliptin price We conclude by summarizing the evidence in favor of HTRA1 and present our hypothesis whereby HTRA1-derived ECM fragments mediate AMD pathogenesis.Evaluating learning outcomes depends upon objective and actionable measures of what students know – that is, what can they do with what they have learned. In the context of a developmental biology course, a capstone of many molecular biology degree programs, I asked students to predict the behaviors of temporal and spatial signaling gradients. Their responses led me to consider an alternative to conventional assessments, namely a process in which students are asked to build and apply plausible explanatory mechanistic models (“PEMMs”). A salient point is not whether students’ models are correct, but whether they “work” in a manner consistent with underlying scientific principles. Analyzing such models can reveal the extent to which students recognize and accurately apply relevant ideas. An emphasis on model building, analysis and revision, an authentic scientific practice, can be expected to have transformative effects on course and curricular design as well as on student engagement and learning outcomes.