Effects of visual processing and congenital nystagmus on visually guided ocular motor behaviour

AIM The aim of this study was to compare visually guided ocular motor behaviour in children with visual processing and/or motor deficits with an age-matched comparison group and an adult group. METHOD Visual stimuli were shown to 28 children with visual processing and/or motor deficits (11 females, 17males; mean age 7y 5mo, SD 2y 9mo, range 2-14y;) and an age-matched comparison group of 213 typically developing children (115 females, 98 males; mean age 5y 8mo, SD 3y 5mo, range 0-12y). The adult group consisted of nine females and two males with (mean age of 24y 4mo, SD 4y 8mo). Individuals who had a likely diagnosis of cerebral visual impairment (CVI), an opticopathy with unknown location, nystagmus, glaucoma, or a cataract were included in the study. Exclusion criteria were a visual acuity below 0.2, a developmental age under 1 year, and the presence of brain tumours, autism, and anxiety disorders. Orientating eye movements to large cartoons were quantified using the reaction time to fixation (RTF) and gaze fixation area (GFA). A Mann-Whitney U test was used to compare the differences between groups and Bonferroni post-hoc testing was used to analyse age dependence of RTF and GFA values within the comparison group. RESULTS Individuals with CVI showed significantly prolonged RTF values; those with congenital nystagmus showed significantly increased GFA values. In the comparison group, RTF was significantly longer in children under the age of 2 years than in children aged 4 years and older (290 and 200ms respectively; p < 0.001). No developmental change was found for GFA values. INTERPRETATION Increased RTF values in individuals with CVI relate to visual processing deficits. The data suggest that visually guided ocular motor responses mature during the first 3 years of life

Orienting Responses to Various Visual Stimuli in Children With Visual Processing Impairments or Infantile Nystagmus Syndrome

Quantification of orienting responses can be used to differentiate between children with cerebral visual impairment and infantile nystagmus syndrome. To further improve the sensitivity of this method, we compared orienting responses to a Cartoon stimulus, which contains all sorts of visual information, to stimuli that contain only Contrast, Form coherence, Motion coherence, Color and Motion detection. The stimuli were shown on an eye tracker monitor using a preferential looking paradigm. We found that both groups of children showed general slowing in orienting responses compared to controls. The children with cerebral visual impairment had significantly prolonged responses to Cartoon compared to the children with nystagmus, whereas the children with nystagmus had prolonged responses to Motion detection and larger fixation areas. Previously reported differences in orienting responses to Cartoon were replicated. Application of specific visual information did not alter the sensitivity of the method to distinguish between children with visual processing deficits

Nephrotoxicity and Kidney Transport Assessment on 3D Perfused Proximal Tubules

Contains fulltext : 194882.pdf (publisher's version ) (Open Access

Nephrotoxicity and Kidney Transport Assessment on 3D Perfused Proximal Tubules

Proximal tubules in the kidney play a crucial role in reabsorbing and eliminating substrates from the body into the urine, leading to high local concentrations of xenobiotics. This makes the proximal tubule a major target for drug toxicity that needs to be evaluated during the drug development process. Here, we describe an advanced in vitro model consisting of fully polarized renal proximal tubular epithelial cells cultured in a microfluidic system. Up to 40 leak-tight tubules were cultured on this platform that provides access to the basolateral as well as the apical side of the epithelial cells. Exposure to the nephrotoxicant cisplatin caused a dose-dependent disruption of the epithelial barrier, a decrease in viability, an increase in effluent LDH activity, and changes in expression of tight-junction marker zona-occludence 1, actin, and DNA-damage marker H2A.X, as detected by immunostaining. Activity and inhibition of the efflux pumps P-glycoprotein (P-gp) and multidrug resistance protein (MRP) were demonstrated using fluorescence-based transporter assays. In addition, the transepithelial transport function from the basolateral to the apical side of the proximal tubule was studied. The apparent permeability of the fluorescent P-gp substrate rhodamine 123 was decreased by 35% by co-incubation with cyclosporin A. Furthermore, the activity of the glucose transporter SGLT2 was demonstrated using the fluorescent glucose analog 6-NBDG which was sensitive to inhibition by phlorizin. Our results demonstrate that we developed a functional 3D perfused proximal tubule model with advanced renal epithelial characteristics that can be used for drug screening studies