We host a series of online journal clubs, highlighting the use and the applications of our OptoDrum device. Scientists present their projects and new data, and you can learn about the latest developments in the field. We always schedule time for Q&A at the end of the presentation so that you can ask your questions and discuss the findings.
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Next online Journal Club
The membrane protein Nogo-A is a potent inhibitor of neuronal growth. After injury, blockade of Nogo-A can support regeneration and functional recovery. For example, in the visual system, the deleterious effects of retinal ischemia on the neuronal survival and function of juvenile mice can be reduced by blocking Nogo-A. In the current study, the aim was to investigate the role of Nogo-A in visual impairments induced by NMDA excitotoxicity in the adult mouse. N-Methyl-D-Aspartate receptor (NMDAR) over-activation is involved in major diseases such as diabetic retinopathy.
Different levels of retinal injury were induced by intravitreal injection of 0.5 to 40 nmol of NMDA. Nogo-A’s function was blocked by using either knock-out (KO) mice or by intraviteally injecting a function-blocking antibody (11C7) two days after NMDA injection. Effects were quantified by following visual function with the optomotor reflex (OMR) and electroretinogram (ERG) recordings, by monitoring visual cortex activity through local field potential (LFP) recording, and by analysing cell survival with immunofluorescence on retinal flat mounts.
Low concentrations of NMDA produced damage limited to the ganglion cell layer (GCL), consisting of a drop of ~20% in visual acuity and a ~30% ganglion cell (GC) loss. Higher concentrations of NMDA resulted in generalized damage to the whole retina: GC loss reached ~80%, visual acuity dropped by ~80% and ERG b-wave amplitudes decreased by half. Nogo-A KO mice, and mice injected with 11C7 intravitreally, showed better functional recovery after NMDA insults. Reduced latency of LFP suggested enhanced visual cortex function after Nogo-A inactivation compared to conrol. However, 11C7 did not significantly influence RGC survival and the ERG response.
Our data suggest that Nogo-A is implicated in the emergence of visual deficits after retinal injury. Antibody-based neutralization of Nogo-A may stimulate visual recovery in retinal diseases involving excitotoxic cell death such as diabetic retinopathy.
- Nogo-A expression is upregulated in human ocular pathologies
- Effects of Nogo-A on neuroinflammation
- Different concentrations of NMDA induce different types of injury and visual deficits.
- Systemic as well as acute and localised neutralisation of Nogo-A improves visual functions after retinal injury.
Nogo-A-targeting antibody promotes visual recovery and inhibits neuroinflammation after retinal injury. Baya Mdzomba J, Joly S, Rodriguez L, Dirani A, Lassiaz P, Behar-Cohen F, Pernet V. Cell Death Dis. 2020 Feb 6;11(2):101.
Nogo-A inactivation improves visual plasticity and recovery after retinal injury. Mdzomba JB, Jordi N, Rodriguez L, Joly S, Bretzner F, Pernet V. Cell Death Dis. 2018 Jun 27;9(7):727.
About the speaker
Julius Baya Mdzomba, PhD
Department of Molecular Medicine, Centre Hospitalier Universitaire de Québec - Université Laval
Julius received his BSc in Cellular Biology in Marsaille, and later specialized in immunological questions of neurodevelopment for his MSc. He has recently received his PhD in Neurobiology from Laval University in Quebec, for his work on the role of Nogo-A in visual deficits, in the lab of Vincent Pernet.
Previous online Journal Club
Visual Acuity as a Relevant Phenotype in Mouse Models of Rare DiseaseZoë Bichler, PhD - The Jackson Laboratory
Maximiliano Presa, PhD - The Jackson Laboratory
The Jackson Laboratory (JAX) is integrating mouse genetics and human genomics to decipher the genetic and molecular causes of human health and disease. JAX supports the global biomedical research community by developping and sharing research, tools and solutions, data resources, and more than 11,000 specialized mouse models.
In today's presentation, we will briefly introduce the Center for Biometric Analysis (CBA), which includes several phenotyping cores, and in particular the Neurobehavior Phenotyping Core (NBP). We show how we have validated visual acuity measurements at the NBP. We will present two projects where visual acuity measurements have been valuable for characterizing progression in rare diseases:
- Validation of visual acuity measurements
- Characterization of new mouse models for human diseases
- Preclinical evaluation of gene therapies
- Understand how JAX validates tests, analyzes data and offers services to researchers.
- Practical applications of visual acuity testing as reliable method for retinopathy assessments.
About the speakers
Zoë Bichler, PhD
Head of the Neurobehavioral Phenotyping Core at the Center for Biometric Analysis
The Jackson Laboratory
Maximiliano Presa, PhD
Technology and Resource Development Scientist
The Jackson Laboratory
My research is focused in the development and characterization of new mouse models for human diseases. We are applying cutting-edge CRISPR/Cas9-based genome editing technology for a precise engineering of the mouse genome with the goal of reproducing human clinical alleles (knock in and knock out models). Together with the generation of transgenic mouse models expressing human gene variants, we are expanding the genetic tools available for the scientific community in areas like ALS, Charcot-Marie-Tooth, lysosomal storage diseases and several others rare disorders. Our validation process starts with a general molecular analysis based on gene expression and protein analysis as well as molecular markers relevant to the disease. The process is followed for a rigorous biometric analysis where we look for survival, growth and behavioral phenotypes. We also complement our analysis with electrophysiology, in vivo imaging and histopathology assessments. Our team is highly specialized in downstream in vivo applications for pre-clinical testing of new compounds and treatments. We have succeeded in pre-clinical gene therapy studies for Charcot-Marie-Tooth-type-4J and currently ongoing gene therapy for multiple sulfatase deficiency (MSD). Thus, we are contributing to the research community with better mouse models and setting new platforms for future development of more precise therapeutic strategies.