2020-2021 Early-career funded researchers
For this second edition, the Network is pleased to announce that it has awarded 5 early-career researchers.
Alexander Baldwin, PhD
Assistant Professor since January 2021
Research Institute of the McGill University Health Center
Axis: Brain and Perception
Domain: Discovery research
Adaptation of visual processing to noisy signals in normal vision and Visual Snow Syndrome
To perceive the world through sight, the visual system must perform sophisticated processing on the input from the eyes. The visual input is noisy, and so the information regarding what is being seen must be inferred. Recent findings suggest that the brain may adapt its processing to the noise in the input. This can be seen in studies of healthy vision, in studies of changes with age, and in disease. This raises the question of whether these proposed adaptations are responsible for some of the symptoms of those diseases. In this project, I set out to establish whether these adaptations occur, with a specific focus on Visual Snow Syndrome. This condition has only recently gained interest as an area of study. Its sufferers experience a “TV static” noise across their visual field. My hypothesis is that in healthy vision there is a homeostatic balance controlling the effects of visual noise. In Visual Snow Syndrome, I would therefore hypothesise that this balance has been disturbed. For example, the palinopsia experienced by some patients may be due to abnormal temporal integration. In my project, I will develop behavioural methods to measure the strength of the visual noise affecting these individuals. I will also develop methods to measure the adaptive responses that this noise may have elicited. These experiments will use online psychophysical testing to reach a large cohort. Should this study find the hypothesised imbalance to be responsible, then that would raise the possibility of “re-balancing” the system to cure the condition.
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Alexandre Reynaud, PhD
Assistant Professeur since January 2021
Research Institute of the McGill University Health Center
Axis: Brain and Perception
Domain: Discovery research
Catch-up the delay in amblyopia treatment
Amblyopia is the first cause of monocular blindness in North America (prevalence 3~5%). The key to treating amblyopia is to restore binocular vision, as it has been shown that the binocular deficit is the primary deficit and the loss of acuity in the amblyopic eye is simply a secondary consequence. The key obstacle to binocular vision in amblyopia is the suppression of the information coming from the amblyopic eye during binocular viewing. This interocular suppression characterizes a lack of binocular combination between the 2 eyes: a lack of cooperation. In fact, there is evidence of a deficit in synchronization (i.e. a neural processing delay) between the two eyes of amblyopes: the greater the amblyopia, the larger the interocular delay. So, what if the 2 eyes don’t cooperate together simply because they don’t work at the same time? Could it then be possible to restore binocular vision by re-synchronizing the 2 eyes inputs? These are the 2 questions I will address in this project. I will first measure the interocular delay using psychophysical methods, and second assess the effect of this delay on binocular combination using electroencephalography. I aim to provide a better understanding of suppression in terms of the synchronicity of neural signals. These new insights that could lead to new and novel treatment to restore binocular function in amblyopia, based on interocular synchronicity.
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The next two projects were also supported by the Fondation Antoine-Turmel.
Christos Boutopoulos, PhD
Assistant Professeur since September 2016
Centre de recherche de l’Hôpital Maisonneuve-Rosemont
Université de Montréal
Axis: Retina and Posterior Segment
Domain: Translational and preclinical research
An OCT-guided system for precise and reproducible subretinal drug injection to mice
Subretinal injection (SI) of gene or cell therapy is a challenging surgical intervention aiming to restore and/or preserve the vision of patients suffering from a broad spectrum of retinal degenerative diseases. To perform a SI, surgeons should insert a cannula into the retina, a delicate tissue layer (200 to 300 μm in humans) and inject a small drug volume. Although this intervention has a crucial role on the overall therapeutic outcome, it has yet to be standardized in animal models. In mice, SI are particularly challenging due to lack of injection tools tailored to the mouse eye anatomy. The associated drug dose administration uncertainty hinders the development of novel treatments. Here, we propose to validate an automated optical coherence tomography (OCT) – guided system for SI in mice. This novel system has the potential to enable unprecedented precision (down to few μm) and reliability in subretinal drug delivery. As such, it could not only help researchers to validate novel treatments but to also target precisely retinal layers. Precise targeting is impossible with established practices as they rely on manual needle insertion and subjective evaluation of the penetration depth.
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Malika Oubaha, PhD (renewal)
Assisant Professor since June 2019
Université du Québec à Montréal (UQAM)
Centre d’excellence en recherche sur les maladies orpheline, Fondation Courtois (CERMO-FC)
Axis: Retina and Posterior Segment
Domain: Discovery research
Role of developmental senescence in vascular plasticity during rare and common retinopathies
Blood vessels are among the first organs to develop in the embryo and are critical for tissue function and homeostasis. Postnatally, arteries and veins are considered terminally differentiated, but they retain enough plasticity to form new blood vessels.
We discovered recently in human mouse retina, senescent cells (that age prematurely) producing a series of factors that contribute to vascular regrowth. Our unpublished data, revealed features of premature senescence in fetal transitory vessels, called hyaloids, in the developing eye, that will regress be replaced by definitive retinal blood vessels. Interestingly, these senescent hyaloids of arterial origin are dynamic and can lose their original identity and acquire a vein identity. How developmental senescence partakes in arteriovenous identity switch during vascular eye development remains unanswered. My long-term goal is to decipher the cellular and molecular mechanisms that initiate and regulate senescence in the developing eye, and determine how this process influences vascular plasticity as needed for vascular growth in homeostatic conditions. Based on solid preliminary data (published and not yet published), this work will test the general hypothesis that senescence is needed in vascular eye remodeling, not only hyaloid vessels regression of but also for the subsequent growth of definitive retinal vessels. This pioneering study of the role of senescence in vascular plasticity hold a lot of promises for new therapeutic targets.
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Stuart Trenholm, PhD
Assistant Professor since August 2017
Montreal Neurological Institute – McGill University
Axis: Brain and Perception / Visual Impairment and Rehabilitation
Domain: Discovery research
Brain circuits underlying spatial navigation following vision loss
Background: As we wander through the world, our visual system provides accurate assessments of our spatial location. Following vision loss, alternative sensory strategies are needed for determining spatial location. However, it remains unclear how the brain’s spatial navigation system adapts following vision loss. To address this issue, in freely moving mice we will record from head direction (HD) cells in the anterior dorsal nucleus of the thalamus in sighted and blind animals, and perform 3 aims:
- Aim 1: Is HD cell tuning impaired in blind animals? To address this, we will record from HD cells in rd1 mice (a model of retinitis pigmentosa who go blind by P30). We provide preliminary results showing intact HD cell tuning in blind animals).
- Aim 2: Is there an effect of the timing of vision loss on the quality of HD cell tuning in blind animals? We will examine HD tuning in two different models of vision loss: rd1 mice, who have normal vision upon eye opening but subsequently go blind; Gnat1/2 mutant mice who have dysfunctional photoreceptors and are congenitally blind.
- Aim 3: What sensory system do blind mice use to guide spatial navigation? In blind mice, we will ablate other sensory systems and examine the effect on HD cell tuning.
These will be the first experiments examining what happens to HD cell tuning in blind animals. These experiments will provide critical insights into how the brain adapts to enable spatial navigation following vision loss.