Image
StriatechJournal Club
Return to overview:  

The role of Nogo-A in visual deficits induced by retinal injury.

Julius Baya Mdzomba, PhD - Université Laval
Cover Baya Paper

Live date was Jan 28th, 2021

Missed the live date? Don't worry!

Scroll down to watch the event.

Watch below

Description

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 intravitreally 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.

Key Topics

  • 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.

Learning Objectives

This presentation aims to show the link between Nogo-A and visual deficits aggravation after retinal injury. Nogo-A is implicated in many processes that would exacerbate any visual deficits after an ocular pathology. Neutralization of Nogo-A is a promising novel therapeutic approach.

Background Reading

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.
doi: 10.1038/s41419-020-2302-x.

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.
doi: 10.1038/s41419-018-0780-x.

About the speaker

Julius Baya Mdzomba, PhD

Julius Baya Mdzomba, PhD

Research Associate - Department of Molecular Medicine, Centre Hospitalier Universitaire de Québec
Université Laval

Image

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.

Watch the Journal Club here

Q&A from the presentation

Here are questions asked during the presentation, and their answers. Please send us an email if you have further questions: info@stria.tech

Other Journal Clubs and Webinars