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

被引：20

作者：

Baya Mdzomba, Julius ^{[1
,2
]}

Joly, Sandrine ^{[1
,2
]}

Rodriguez, Lea ^{[1
,2
]}

Dirani, Ali ^{[1
,2
]}

Lassiaz, Patricia ^{[3
,4
]}

Behar-Cohen, Francine ^{[3
,4
]}

Pernet, Vincent ^{[1
,2
]}

机构：

[1] Univ Laval, CUO Rech, Ctr Rech, CHU Quebec, Quebec City, PQ, Canada

[2] Univ Laval, Fac Med, Dept Ophtalmol, Quebec City, PQ, Canada

[3] Paris Descartes Univ, Sorbonne Univ, Inserm, UMR S 1138,Team 17,Ctr Rech Cordeliers, Paris, France

[4] Univ Paris 06, Paris, France

来源：

CELL DEATH & DISEASE | 2020年 / 11卷 / 02期

基金：

加拿大创新基金会;

关键词：

OPTOKINETIC RESPONSE; AXONAL REGENERATION; NEURITE OUTGROWTH; CELL ACTIVATION; ADULT-RAT; IN-VIVO; KAPPA-B; GLUTAMATE; RECEPTOR; PROTEIN;

D O I：

10.1038/s41419-020-2302-x

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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 TNF alpha was the most durably decreased cytokine in microglia/macrophages. Additional analyses suggest that TNF alpha 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.

引用

页数：16

共 68 条

[11] Identification of a receptor mediating Nogo-66 inhibition of axonal regeneration [J].