Nogo-A-targeting Antibody Promotes Visual Recovery and Inhibits Neuroinflammation After Retinal Injury

Overview

Journal Cell Death Dis

Specialties Cell Biology
General Medicine

Date 2020 Feb 8

PMID 32029703

Citations 13

Authors

Julius Baya Mdzomba

Sandrine Joly

Lea Rodriguez

Ali Dirani

Patricia Lassiaz

Francine Behar-Cohen

Vincent Pernet

Affiliations

Soon will be listed here.

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.

Citing Articles

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Anti-inflammatory Effects of Siponimod in a Mouse Model of Excitotoxicity-Induced Retinal Injury.

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Nogo-A and LINGO-1: Two Important Targets for Remyelination and Regeneration.

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