Interactive digital technologies are currently being developed as a novel tool for education and skill development. Audiopolis is an audio and haptic based videogame designed for developing orientation and mobility (O&M) skills in people who are blind. We have evaluated the cognitive impact of videogame play on O&M skills by assessing performance on a series of behavioral tasks carried out in both indoor and outdoor virtual spaces. Our results demonstrate that the use of Audiopolis had a positive impact on the development and use of O&M skills in school-aged learners who are blind. The impact of audio and haptic information on learning is also discussed.
The importance of cell types in understanding brain function is widely appreciated but only a tiny fraction of neuronal diversity has been catalogued. Here we exploit recent progress in genetic definition of cell types in an objective structural approach to neuronal classification. The approach is based on highly accurate quantification of dendritic arbor position relative to neurites of other cells. We test the method on a population of 363 mouse retinal ganglion cells. For each cell, we determine the spatial distribution of the dendritic arbors, or arbor density, with reference to arbors of an abundant, well-defined interneuronal type. The arbor densities are sorted into a number of clusters that is set by comparison with several molecularly defined cell types. The algorithm reproduces the genetic classes that are pure types, and detects six newly clustered cell types that await genetic definition.
EGFL7 is a secreted angiogenic factor, which in contrast to the well-known secreted angiogenic molecules VEGF and FGF-2, is almost exclusively expressed by endothelial cells and may act in an autocrine fashion. Prior studies have shown EGFL7 to mediate its angiogenic effects by interfering with the Notch pathway and/or via the intronic miR126. Less is known about its effects on VEGF signaling. We wanted to investigate the role of epidermal growth factor-like domain 7 (EGFL7) in VEGF-driven angiogenesis using an ex vivo Matrigel-embedded mouse eye cup assay and siRNA mediated knockdown of EGFL7 by siRNA. Our results suggested that VEGF-induced vascular tube formation was significantly impaired after siRNA downregulation of EGFL7. In addition, knockdown of EGFL7 suppressed VEGF upregulation of phospho-Akt and phospho-Erk(1/2) in endothelial cells, but did not alter VEGFR phosphorylation and neuropilin-1 protein expression or miR126 expression. Thus, in conclusion, EGFL7 is required for VEGF upregulation of the Akt/Erk (1/2) pathway during angiogenesis, and may represent a new therapeutic target in diseases of pathological neovascularization.
A 24-year-old woman underwent excision of a slowly growing mass located in the right superomedial orbit that had histopathologic and immunohistochemical findings consistent with a choristomatous respiratory cyst. This rare condition may either arise primarily from embryologic respiratory epithelium rests in the orbit or develop secondarily as the result of trauma or chronic sinus disease complicated by mucocele formation.
Neuroprotection is an emerging challenge in ophthalmology due to the particularly exposed location of retinal neurons and to the steadily increasing rate of intraocular surgical and pharmacological treatments applied to various eye diseases. Within few decades neuroprotection has developed from strongly contested approaches to being recognized and introduced as a potentially clinical application. One of the groups of putative substances for neuroprotection comprises αA- and αB-crystallins, which are types of heat-shock proteins and are considered to be molecular chaperones. The β/γ-crystallins form their own superfamily and are characterized as proteins with a distinct structure containing four Greek key motifs. Besides being abundant in the ocular lens, crystallins are also expressed in both the developing and mature retina. Crystallins are dramatically up-regulated in numerous retinal pathologies, including mechanical injury, ischemic insults, age-related macular degeneration, uveoretinitis, and diabetic retinopathy. Crystallins of the α family are thought to play a crucial role in retinal neuron survival and inflammation. Crystallins of the β/γ superfamily are also small proteins with a possible emerging role in retinal tissue remodeling and repair. One of the typical retinal diseases associated with crystallins is the experimental glaucomatous neuropathy that is characterized by their expression. Another typical retinal disease is the atrophy that occurs after mechanical injury to the optic nerve, which is associated with the need to regrow retinal axons. We have shown in regenerative models in vivo and in vitro that βB2-crystallin actively supports the regenerative growth of cut retinal axons, thereby offering targets for neuroprotective and regenerative treatments. In this review we discuss the discovery that βB2-crystallin is clearly up-regulated in the regenerating retina in vitro. βB2-Crystallin is produced and secreted during axon elongation, while β/γ-crystallins promote axon growth both in vivo and in vitro by acting either directly by uptake into cells, or indirectly by enhancing the production of ciliary neurotrophic factor from astrocytes to synergistically promote axon regrowth. We also discuss methods to induce the continuous production of crystallins at the site of injury and repair based on the use of transfected neural progenitor cells. This review ultimately leads to the conclusion that the postinjury fate of neurons cannot be seen merely as inevitable, but instead should be regarded as a challenge to shaping the neuroprotective and regenerative conditions that promote cell survival and axon repair.
Autosomal-dominant idiopathic infantile nystagmus has been linked to 6p12 (OMIM 164100), 7p11.2 (OMIM 608345) and 13q31-q33 (OMIM 193003). PAX6 (11p13, OMIM 607108) mutations can also cause autosomal-dominant nystagmus, typically in association with aniridia or iris hypoplasia. We studied a large multigenerational white British family with autosomal-dominant nystagmus, normal irides and presenile cataracts. An SNP-based genome-wide analysis revealed a linkage to a 13.4-MB region on chromosome 11p13 with a maximum lod score of 2.93. A mutation analysis of the entire coding region and splice junctions of the PAX6 gene revealed a novel heterozygous missense mutation (c.227C>G) that segregated with the phenotype and is predicted to result in the amino-acid substitution of proline by arginine at codon 76 p.(P76R). The amino-acid variation p.(P76R) within the paired box domain is likely to destabilise the protein due to steric hindrance as a result of the introduction of a polar and larger amino acid. Eye movement recordings showed a significant intrafamilial variability of horizontal, vertical and torsional nystagmus. High-resolution in vivo imaging of the retina using optical coherence tomography (OCT) revealed features of foveal hypoplasia, including rudimentary foveal pit, incursion of inner retinal layers, short photoreceptor outer segments and optic nerve hypoplasia. Thus, this study presents a family that segregates a PAX6 mutation with nystagmus and foveal hypoplasia in the absence of iris abnormalities. Moreover, it is the first study showing detailed characteristics using eye movement recordings of autosomal-dominant nystagmus in a multigenerational family with a novel PAX6 mutation.
We introduce a new task for exploring the relationship between action and attention. In this interactive multiple object tracking (iMOT) task, implemented as an iPad app, participants were presented with a display of multiple, visually identical disks which moved independently. The task was to prevent any collisions during a fixed duration. Participants could perturb object trajectories via the touchscreen. In Experiment 1, we used a staircase procedure to measure the ability to control moving objects. Object speed was set to 1°/s. On average participants could control 8.4 items without collision. Individual control strategies were quite variable, but did not predict overall performance. In Experiment 2, we compared iMOT with standard MOT performance using identical displays. Object speed was set to 2°/s. Participants could reliably control more objects (M = 6.6) than they could track (M = 4.0), but performance in the two tasks was positively correlated. In Experiment 3, we used a dual-task design. Compared to single-task baseline, iMOT performance decreased and MOT performance increased when the two tasks had to be completed together. Overall, these findings suggest: 1) There is a clear limit to the number of items that can be simultaneously controlled, for a given speed and display density; 2) participants can control more items than they can track; 3) task-relevant action appears not to disrupt MOT performance in the current experimental context.
Schlemm's canal is an important structure of the conventional aqueous humor outflow pathway and is critically involved in regulating the intraocular pressure. In this study, we report a novel finding that prospero homeobox protein 1 (Prox-1), the master control gene for lymphatic development, is expressed in Schlemm's canal. Moreover, we provide a novel in vivo method of visualizing Schlemm's canal using a transgenic mouse model of Prox-1-green fluorescent protein (GFP). The anatomical location of Prox-1⁺ Schlemm's canal was further confirmed by in vivo gonioscopic examination and ex vivo immunohistochemical analysis. Additionally, we show that the Schlemm's canal is distinguishable from typical lymphatic vessels by lack of lymphatic vessel endothelial hyaluronan receptor (LYVE-1) expression and absence of apparent sprouting reaction when inflammatory lymphangiogenesis occurred in the cornea. Taken together, our findings offer new insights into Schlemm's canal and provide a new experimental model for live imaging of this critical structure to help further our understanding of the aqueous humor outflow. This may lead to new avenues toward the development of novel therapeutic intervention for relevant diseases, most notably glaucoma.
PURPOSE: Evaluate predictors and outcomes of ocular hypertension after open-globe injury. PATIENTS AND METHODS: This is a retrospective, case-control study reviewing records of consecutive patients with open-globe injuries treated at Massachusetts Eye and Ear Infirmary between February 1999 and January 2007. Of 658 patients treated, 382 had at least 2 months of follow-up and sufficient data to be included. Main outcome measures are visual acuity, intraocular pressure (IOP), and type of glaucoma intervention employed. RESULTS: Sixty-five (17%) patients developed ocular hypertension defined as IOP≥22 mm Hg at >1 visit or requiring treatment. Increased age (P<0.001), hyphema (0.025), lens injury (P<0.0001), and zone II injury (P=0.0254) are risk factors for developing ocular hypertension after open-globe injury. Forty-eight (74%) patients with ocular hypertension were treated medically, 8 (12%) underwent filtering or glaucoma drainage device surgery, 5 (8%) had IOP normalization with observation, while 4 (6%) required anterior chamber washout with no other glaucoma surgery. Patients with ocular hypertension had an average maximum IOP=33.4 mm Hg at a median follow-up of 21 days, with most patients maintaining normal IOP at all follow-up time points. Visual acuity improved over time with median acuity of hand motions preoperatively, and 20/60 at 12 and 36 months. CONCLUSIONS: Ocular hypertension is a significant complication after open-globe injury that sometimes requires surgical intervention. Predictive factors can alert physicians to monitor for elevated IOP in the first month after trauma. Most patients with traumatic ocular hypertension had improved visual acuity and IOP normalization over time.
PURPOSE: To estimate the impact of dry eye disease (DED) on work performance and productivity in office workers using visual display terminals (VDTs). DESIGN: Cross-sectional study. METHODS: Six hundred seventy-two Japanese young and middle-aged office workers using VDTs completed a questionnaire that was designed to measured at-work performance deficits and productivity losses using the Japanese version of the Work Limitations Questionnaire, completed by e-mail. Using the Japanese dry eye diagnostic criteria, respondents were classified into 3 groups: definite DED, probable DED, and non DED. RESULTS: Of the 672 office workers, 553 subjects (82.3%), including 366 men and 187 women, completed the questionnaire and underwent clinical evaluation. As for the total workplace productivity loss, the non DED group demonstrated a loss of 3.56%, those with probable DED demonstrated a loss of 4.06%, and those with definite DED demonstrated a loss of 4.82%, indicating significantly worse performance and productivity (P = .014, trend test). For the 4 subscales, DED was associated with significantly lower on-the-job time management (P = .009, trend test) and combined mental performance and interpersonal functioning (P = .011, trend test). After controlling for age, sex, VDT working hours, and diagnosis of DED, time management, physical demands, and mental and interpersonal functioning showed a significant relationship to DED (each P > .05). Annual DED productivity losses were estimated to be $6160 per employee when measured by total production and $1178 per employee calculated by wage. CONCLUSIONS: This study indicated that there is a significant impact of DED on the total productivity of Japanese VDT users.
