Nogo-A-targeting antibody promotes visual recovery and inhibits neuroinflammation after retinal injury.

TitleNogo-A-targeting antibody promotes visual recovery and inhibits neuroinflammation after retinal injury.
Publication TypeJournal Article
Year of Publication2020
AuteursMdzomba, JBaya, Joly, S, Rodriguez, L, Dirani, A, Lassiaz, P, Behar-Cohen, F, Pernet, V
JournalCell Death Dis
Volume11
Issue2
Pagination101
Date Published2020 Feb 06
ISSN2041-4889
Abstract

N-Methyl-D-aspartate (NMDA)-induced neuronal cell death is involved in a large spectrum of diseases affecting the brain and the retina such as Alzheimer's disease and diabetic retinopathy. Associated neurological impairments may result from the inhibition of neuronal plasticity by Nogo-A. The objective of the current study was to determine the contribution of Nogo-A to NMDA excitotoxicity in the mouse retina. We observed that Nogo-A is upregulated in the mouse vitreous during NMDA-induced inflammation. Intraocular injection of a function-blocking antibody specific to Nogo-A (11C7) was carried out 2 days after NMDA-induced injury. This treatment significantly enhanced visual function recovery in injured animals. Strikingly, the expression of potent pro-inflammatory molecules was downregulated by 11C7, among which TNFα was the most durably decreased cytokine in microglia/macrophages. Additional analyses suggest that TNFα downregulation may stem from cofilin inactivation in microglia/macrophages. 11C7 also limited gliosis presumably via P.Stat3 downregulation. Diabetic retinopathy was associated with increased levels of Nogo-A in the eyes of donors. In summary, our results reveal that Nogo-A-targeting antibody can stimulate visual recovery after retinal injury and that Nogo-A is a potent modulator of excitotoxicity-induced neuroinflammation. These data may be used to design treatments against inflammatory eye diseases.

DOI10.1038/s41419-020-2302-x
Alternate JournalCell Death Dis
PubMed ID32029703
PubMed Central IDPMC7005317
Grant List407687 / / Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada) /
34204 / / Canada Foundation for Innovation (Fondation canadienne pour l'innovation) /