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: Stereoscopic Vision uses the disparity between the two images received by the two eyes in order to create a tridimensional representation. With this study, we aimed at providing an estimate of binocular vision at a level prior to disparity processing. In particular, we wanted to assess the spatial properties of the visual system for detecting interocular correlations (IOC).
Methods: We developed dichoptic stimuli, made of textures which IOC is sinusoidally modulated at various correlation spatial frequencies. Then, we compared the sensitivity to these stimuli to the sensitivity to analogous stimuli with disparity modulation.
Results: We observed that IOC sensitivity presents a low-pass/band-pass profile and increases as a function of presentation duration and contrast, in a similar way as disparity sensitivity.
Conclusions: IOC sensitivity is weakly—though significantly—correlated with disparity sensitivity in the general population, which suggests that it could provide a marker for binocular vision, prior to disparity processing.
Background: The perception of visual forms is crucial for effective interactions with our environment and for the recognition of visual objects. Thus, to determine the codes underlying this function is a fundamental theoretical objective in the study of the visual forms perception. The vast majority of research in the field is based on a hypothetico-deductive approach. Thus, we first begin by formulating a theory, then we make predictions and finally we conduct experimental tests. After decades of application of this approach, the field remains far from having a consensus as to the traits underlying the representation of visual form. Our goal is to determine, without theoretical a priori or any bias whatsoever, the information underlying the discrimination and recognition of 3D visual forms in normal human adults.
Methods: To this end, the adaptive bubble technique developed by Wang et al. [2011] is applied on six 3D synthetic objects under varying views from one test to another. This technique is based on the presentation of stimuli that are partially revealed through Gaussian windows, the location of which is random and the number of which is established in such a way as to maintain an established performance criterion. Gradually, the experimental program uses participants’ performance to determine the stimulus regions that participants use to recognize objects. The synthetic objects used in this study are unfamiliar and were generated from a program produced at C. Edward Connor’s lab, Johns Hopkins University School of Medicine.
Results: The results were integrated across participants to establish regions of presented stimuli that determine the observers’ ability to recognize them—i.e., diagnostic attributes. The results will be reported in graphical form with a Z scores mapping that will be superimposed on silhouettes of the objects presented during the experiment. This mapping makes it possible to quantify the importance of the different regions on the visible surface of an object for its recognition by the participants.
Conclusions: The diagnostic attributes that have been identified are the best described in terms of surface fragments. Some of these fragments are located on or near the outer edge of the stimulus while others are relatively distant. The overlap is minimal between the effective attributes for the different points of view of the same object. This suggests that the traits underlying the recognition of objects are specific to the point of view. In other words, they do not generalize through the points of view.
Background: The concept of stochastic facilitation suggests that the addition of precise amounts of white noise can improve the perceptibility of a stimulus of weak amplitude. We know from previous research that tactile and auditory noise can facilitate visual perception, respectively. Here we wanted to see if the effects of stochastic facilitation generalise to a reaction time paradigm, and if reaction times are correlated with tactile thresholds. We know that when multiple sensory systems are stimulated simultaneously, reaction times are faster than either stimulus alone, and also faster than the sum of reaction times (known as the race model).
Methods: Five participants were re-tested in five blocks each of which contained a different background noise levels, randomly ordered across sessions. At each noise level, they performed a tactile threshold detection task and a tactile reaction time task.
Results: Both tactile threshold and tactile reaction times were significantly affected by the background white noise. While the preferred amplitude for the white noise was different for every participant, the average lowest threshold was obtained with white noise presented binaurally at 70 db. The reaction times were analysed by fitting an ex-Gaussian, the sum of a Gaussian function and an exponential decay function. The white noise significantly affected the exponential parameter (tau) in a way that is compatible with the facilitation of thresholds.
Conclusions: We therefore conclude that multisensory reaction time facilitation can, at least in part, be explained by stochastic facilitation of the neural signals.
Background: Saccades are rapid and abrupt eye movements that allow us to change the point of fixation very quickly. Saccades are generally made to visual points of interest, but we can also saccade to non-visual objects that attract our attention. While there is a plethora of studies investigating saccadic eye movements to visual targets, there is very little evidence of how eye movement planning occurs when individuals are performing eye movements to non-visual targets across different sensory modalities.
Methods: Fifteen adults with normal, or corrected to normal, vision made saccades to either visual, auditory, tactile or proprioceptive targets. In the auditory condition a speaker was positioned at one of eight locations along a circle surrounding a central fixation point. In the proprioceptive condition the participant’s finger was placed at one of the eight locations. In the tactile condition participants were touched on their right forearm in one of four eccentric location, left and right of a central point. Eye movements were made in complete darkness.
Results: We compared the precision and accuracy of the eye movements to tactile, proprioceptive, and auditory targets in the dark. Overall, both precision and accuracy of movements to non-visual targets were significantly lower compared to visual targets.
Conclusions: These differences emphasize the central role of the visual system in saccade planning.
