Background: The purpose of this infrastructure is to provide to the Network researchers a database and diverse related tools for the anatomical and functional analysis of the normal, pathological and surgical cornea.
Methods: This database is composed of normal and pathological individuals, totaling more than 36,000 patients. It includes anatomical and functional imaging data, physiological optics data, psychometric and clinical data (medical history, surgical parameters, acuteness, etc.). Various corneal topography tools were added, giving the database a unique character: tools for analyzing individual maps, average map tools for the study and comparison of populations, 3D modeling and visualization tools, statistical tools, etc. There are also screening tools for detecting various corneal conditions (LASIK, PRK, RK, keratoconus) and for secure data exchange between colleagues.
Results: Several studies were made in recent years thanks to this common infrastructure. For example, this database has provided important information regarding the evolution of the 3D shape of the normal cornea with age and ametropia and has confirmed the mirror symmetry of corneas for the right and the left eyes (enantiomorphism). The different stages of Fuchs’ dystrophy were also characterized to provide essential knowledge for surgery of the posterior layer of the cornea. Our database also allowed studying the anatomy of the wounds and the shape of the cornea before and after a transfixing transplant or an endothelial transplant (DSAEK and DSEK). The data on the characterization of experimentally transplanted corneas with corneal equivalents generated by tissue engineering and the recent addition of clinical data on the replacement of a diseased cornea with a synthetic corneal equivalent (keratoprosthesis) also resulted in several publications. More recently, the database has allowed to develop innovative algorithms to determine the optimal shape of an implant according to the clinical parameters of the recipient. On the other hand, we also demonstrated that the 3D shape of the cornea can be used as a biometric characteristic (such as fingerprints) for identification of individuals for various applications ranging from forensics to secure border crossings. Consequently, a new multimodal database (cornea + iris + eventually retina) was created for the purpose of biometric identifications. This database provides a unique set of anatomical and functional tools for the analysis of the cornea. It is characterized by the scientific quality and large quantity of accumulated information on the cornea and the high-level tools to exploit its content.
Conclusions: The common infrastructure is easily accessible to all VHRN members on request. The database will also be accessible online in 2018 (see http://cvl.concordia.ca for more information).
Background: Because of its superficial anatomical localization, the cornea is particularly vulnerable to abrasive forces and various traumas, which can lead to significant visual impairments. Upon injury of the corneal epithelium, there are important changes that occur in the composition of the underlying extracellular matrix (ECM). Those changes are perceived by the integrins that recognize the ECM components as their ligand and activate different intracellular signalling pathways, ultimately leading to reepithelialisation and reorganization of the injured epithelium, both of which are necessary in order to restore the visual properties of the cornea. The goal of this study was to analyse the impact of the pharmacological inhibition of specific signal transduction mediators of integrin-dependant signalling pathways on corneal wound healing using both monolayers of hCECs and tissue-engineered human corneas (hTECs) as in vitro models.
Methods: hTECs were produced by the self-assembly approach and wounded with a 8-mm diameter biopsy punch. Total RNA and proteins were isolated from the wounded and unwounded hTECs to conduct gene profiling analyses and protein kinase arrays. The wounded tissues were then incubated with the WNK1 inhibitor WNK463 and wound healing was monitored over a period of 6 days. Control corneas were incubated with the vehicle alone (DMSO). The impact of WNK1 inhibition on hCECs monolayers was determined using a scratch wound assay.
Results: Gene profiling analyses and protein kinases arrays revealed important alterations in the expression and activity of several mediators from the integrin-dependent signalling pathways in response to the ECM changes taking place during corneal wound healing. Among these, WNK1 is considerably activated through phosphorylation during corneal wound healing. The pharmacological inhibition of WNK1 by WNK463 significantly reduced the dynamic of corneal wound closure in our hTECs and hCECs monolayers compared to their respective negative controls.
Conclusions: These results allowed the identification of WNK1 kinase as an important player for a proper healing of the cornea. Also, these results allowed for a better understanding of the cellular and molecular mechanisms involved in corneal wound healing and they may lead to the identification of new therapeutic targets in the field of corneal wounds.
Background: Congenital hereditary endothelial dystrophy (CHED) is characterized by blindness at birth or in early infancy resulting from bilateral corneal opacification, and is linked to mutation in the Slc4a11 gene. A Slc4a11 knockout (KO) mouse, generated by gene deletion (Vithana et al. Nat Genet 2006), was acquired in order to study this disease. To confirm the phenotype of this Slc4a11 KO mouse model as a function of age, using the wild type (WT) mouse as a control.
Methods: Genotyping was performed by PCR (REDExtract-N-AmpTM Tissue PCR Kit, Sigma-Aldrich, Oakville, ON). Slc4a11 WT and KO mice populations aged from 5 to 50 weeks were studied (n=5 animals per age group; 5-year age intervals). Slit lamp examination, anterior segment-ocular coherence tomography (OCT930SR; Thorlabs, Inc., Newton, NJ), corneal endothelial cell staining, and scanning (SEM) and transmission (TEM) electron microscopy were used to assess the morphological and cellular differences between the two groups. The expression of basolateral membrane transporter NaBC1 within the corneal endothelium was also assessed using immunohistochemistry.
Results: Diffuse and progressive corneal opacification was observed at the slit lamp in the Slc4a11 KO mice, starting at 10 weeks. The central corneal thickness (CCT) also increased progressively as a function of time. In comparison, Slc4a11 WT corneas remained clear over the entire study period. Early TEM results showed vacuole degeneration of the corneal endothelium in the 15-week KO mouse, which was not seen in the same age WT mouse.
Conclusions: The corneal phenotype of this Slc4a11 KO mouse is representative of the clinical manifestations of CHED in human subjects, confirming the usefulness of this model for studying pathophysiology and therapeutic alternatives for Slc4a11-associated corneal dystrophies.
Background: Understanding factors that contribute to posterior capsular opacification (PCO) development is a significant public concern as treatment can lead to complications. In order to prevent PCO, a better understanding of intraocular lens (IOL) characteristics, including design and material, and patient interaction is required. Herein, we performed a retrospective multivariable analysis to determine which factors (IOL and patient based) were least likely to result in PCO.
Methods: One hundred eighty post-mortem eyes with implanted IOLs were collected from the Minnesota Eye Bank, along with clinical history, including date of cataract surgery and IOL model number. The capsular bag (CB) with the IOL implant was removed from all eyes to obtain digital images. PCO outcome was quantified on CB images using an objective, automated custom image analyzer (Medical Parachute Automated Detector Opacification Software). The software measured intensity and area of the opacification within the IOL optic edge, intra-optic edge (IOE = intensity/area), and in Soemmering’s ring (SR = intensity/area). Epidemiologic analysis assessed which IOL characteristics and patient-related factors correlated with PCO. IOL factors included material, edge design, lens filter, company, IOL model, decentration and time from cataract surgery to death. Patient factors included sex, age and diabetes, among others.
Results: Multivariate analyses showed non-diabetic patients had less PCO (P=0.05). Individuals 50–80 years old compared to 80+ had lower SR PCO (P=0.04). Non-blue light filter IOLs had lower SR and IOE PCO compared to filter IOLs (P=0.03, 0.001). Square and frosted optic edge design had lower SR and IOE PCO rates compared to OptiEdge and round optic edge design (P=0.002, 0.02). The IOL model that had the least PCO was the ZA9003 model, but this was only significant for SR and not IOE PCO (P=0.04). Adjusting for patient-factors, IOL lens model was no longer a confounding factor for PCO. Patients with an IOL implanted for <7 years had lower SR PCO, whereas lower IOE PCO was only seen in implants <4 years old (P=0.0001, 0.04).
Conclusions: In order to generate a lens that does not develop PCO, it is critical to understand the IOL- and patient-related factors that lead to PCO development. Based on our data, the most susceptible patients are elderly and diabetic, and it may be preferable to implant a square and frosted edge lens without blue-light filtering in this cohort.
Background: The guiding principle of functional brain mapping is that the cortex exhibits a spatial pattern of response reflecting its underlying functional organization. We know that large-scale patterns are common across individuals—everyone roughly has the same visual areas for example, but we do not know about small patterns, like the distribution of ocular dominance and orientation columns. Studies investigating the temporal aspect of brain-to-brain similarity have shown that a large portion of the brain is temporally synchronized across subjects (Hasson et al., 2004), but spatial pattern similarity has been scarcely studied, let alone at a fine scale. In the current study, we investigated fine-scale spatial pattern similarity between subjects during movie viewing and generated a map of prototypical patterns spanning the visual system. Characteristics of the map, such as spatial pattern size and distribution, reveal properties of the underlying structure and organisation of the visual cortex. These results will guide future brain mapping studies in decoding the informative spatial patterns of the visual cortex and increasing the resolution of current brain maps.
Methods: We had 56 subjects watch two movie clips from “Under the Sea 3D:IMAX” during an fMRI scan. Each clip was 5 minutes in length and was presented in 2D and 3D, in random order. We calculated the intersubject correlation of the spatial pattern inside predefined searchlights of diameter 3, 5, 7, 9 and 11 mm, covering the entire brain. A single threshold permutations test was used to test for significance: we generated 1,000 permutations made from scrambling the spatial patterns inside each searchlight of every subject, pooled these permutations together to generate a large distribution and used the 95th percentile to threshold the actual measurements. We compared these spatial pattern correlations to convexity variance between subjects to determine whether spatial pattern correlation could be explained by differing degrees of alignment across the cortex. We also compared spatial pattern correlation during 2D and 3D movie presentation.
Results: We found significant correlations in spatial pattern between subjects in the majority of early visual cortex, as well as higher visual areas. We found that mean spatial pattern similarity in a visual area tended to decrease as we move up the visual hierarchy. Spatial pattern correlation showed significant positive correlation with convexity variance for most visual areas, meaning that as anatomical misalignment increased, patterns became more similar. Spatial pattern correlation therefore cannot be explained by anatomical misalignment. Lastly, spatial pattern correlations tended to be higher for 3D movie presentation compared to 2D.
Conclusions: Our results suggest that many processes in early visual areas and even higher visual areas process visual information the same way in different individuals. Our results expand past studies by exploring spatial patterns instead of temporal patterns and studying at a fine-scale. This is the first study, to our knowledge, exploring fine-scale spatial patterns across the visual system. Our results show that fine-scale structures underlying activation patterns may be highly similar across subjects, pointing to a more ingrained organisation of the visual system than previously believed. This map we termed the “protoSPACE map”, may one day result in the detection of more subtle abnormalities that arise only during realistic vision in situations such as schizophrenia or mild traumatic brain injury, where traditional anatomical MRI scans report no changes.
Background: Cognitive control is defined as the ability to act flexibly in the environment by either behaving automatically or inhibiting said automatic behaviour and it can be measured using an interleaved pro/anti-saccade task. Decline in cognitive control has been attributed to normal aging and neurological illnesses such as Parkinson’s disease (PD) as well as decline in other cognitive abilities. This parallel might highlight the role played by cognitive control in information processing and working memory. However, little is known about the relationship between cognitive control and other cognitive processes such as visual memory, decision making, and visual search. We thus propose to correlate the incidence of impaired cognitive control with deficits in visual memory, decision making and visual search in three groups: younger adults, older adults and patients with idiopathic PD.
Methods: Seventy-one participants, namely 34 adults (M =22.75, SD =3.8), 22 older adults (M =67.4, SD =8.3), and 20 PD patients (M =65.59, SD =8.2) performed four tasks: interleaved pro/anti-saccade, visual memory, decision making, and serial and pop-out visual search.
Results: Results show that within each group, anti-saccade error rate (ER) were significantly and negatively correlated with visual memory ER (ryounger =?0.378, P=0.036; rolder =?0.440, Polder =0.046; rPD =?0.609, P=0.016). On the other hand, correct decision-making reaction times (RT) were significantly correlated with anti-saccade ER, and RTs only in older adults (rER =0.529, P=0.014; rRT =0.512, P=0.018) and PD patients (rER =0.727, P=0.012; rRT =0.769, P=0.001). For visual search, PD patients showed a significant relationship between RTs for correct pro-saccades and pop-out (r=0.665, P=0.007), and serial (r=0.641, P=0.010) search RTs. Furthermore, there was a significant correlation between MoCA scores and anti-saccade RTs (r=?0.559, P=0.030) and ER (r=?0.562, P=0.029) in PD patients. Taken together, these results support the hypothesis of PD patients’ reliance on bottom-up processes as top-down processes decline. For younger adults, there was a significant correlation between serial search performance and both anti-saccade ER (r=0.488, P=0.005), and correct pro-saccade ER (r=0.413, P=0.021). In older adults, this relationship was absent, but anti-saccade ER significantly correlated with pop-out search times (r=0.473, P=0.030).
Conclusions: We found significant relationships between cognitive tasks and cognitive control as measured through the interleaved pro/anti-saccade task across and within participant groups, providing evidence of the appropriateness of the use of the interleaved pro/anti-saccade task as a measure of overall cognitive control.
Background: Understanding how individuals with autism spectrum disorder (ASD) learn is important for developing and implementing effective educational and behavioral interventions. Evidence suggests that individuals with ASD are relatively stronger in certain areas of perception (Simmons et al., 2009; Dakin and Frith, 2005); it therefore cannot be assumed that individuals with ASD learn using the same rules and strategies as neurotypicals (NT). Of particular interest, perceptual learning (PL) is a class of learning that is based upon changes induced by the repeated exposure and response to specific types of perceptual information. Such learning often includes feedback, indicating whether or not a response was correct during a trial within a PL task. The objectives of this study were to perform a pilot investigation of; (I) perceptual learning in adults with and without ASD using a low-level orientation discrimination task; and (II) the influence of feedback on accuracy in this task.
Methods: Eleven adults with ASD and fifteen NT adults, matched on Wechsler full-scale IQ and age (18–31 years), performed a low-level PL task. They were asked to indicate whether a grating was tilted to the left (i.e., counter-clockwise) or to the right (i.e., clockwise) relative to an oblique 45-degree reference orientation. Thresholds, defined by the minimal deviation in degrees needed to discriminate tilt orientation, were measured for each participant every 15 minutes, with each block consisting of 420 trials. To assess baseline performance, all participants completed a first block with no feedback. Participants were then randomly assigned to either feedback (NASD =6, NTD =8) or no feedback groups (NASD =5, NTD =7) and completed six subsequent testing blocks.
Results: PL was defined as the percent change in orientation discrimination threshold in each of the six testing blocks relative to baseline performance. No significant increase was found in performance as a function of testing block for any group; PL was therefore not evidenced under the conditions tested. ASD performance remained equal to that of baseline across testing blocks, whether or not trial-by-trial feedback was present. In contrast, NT performance was significantly increased when feedback was present.
Conclusions: NT individuals significantly benefited from feedback, while individuals with ASD did not. These results provide preliminary evidence for a divergent learning style in ASD and NT individuals. These pilot findings raise important questions regarding the impact of feedback during interventions, and at a more basic level, the atypical underlying perceptual and cognitive processes in individuals with ASD.
