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

[1] Schwann cell-derived factor-induced modulation of the NgR/p75NTR/EGFR axis disinhibits axon growth through CNS myelin in vivo and in vitro [J].

Ahmed, Zubair ;

Suggate, Ellen L. ;

Brown, Elspeth R. ;

Dent, Russell G. ;

Armstrong, Stephanie J. ;

Barrett, Lee B. ;

Berry, Martin ;

Logan, Ann .

BRAIN, 2006, 129 :1517-1533

[2] Cofilin Mediates LPS-Induced Microglial Cell Activation and Associated Neurotoxicity Through Activation of NF-κB and JAK-STAT Pathway [J].

Alhadidi, Qasim ;

Shah, Zahoor A. .

MOLECULAR NEUROBIOLOGY, 2018, 55 (02) :1676-1691

[3] Elevated gamma-aminobutyric acid, glutamate, and vascular endothelial growth factor levels in the vitreous of patients with proliferative diabetic retinopathy [J].

Ambati, J ;

Chalam, KV ;

Chawla, DK ;

DAngio, CT ;

Guillet, EG ;

Rose, SJ ;

Vanderlinde, RE ;

Ambati, BK .

ARCHIVES OF OPHTHALMOLOGY, 1997, 115 (09) :1161-1166

[4] Neural apoptosis in the retina during experimental and human diabetes - Early onset and effect of insulin [J].

Barber, AJ ;

Lieth, E ;

Khin, SA ;

Antonetti, DA ;

Buchanan, AG ;

Gardner, TW .

JOURNAL OF CLINICAL INVESTIGATION, 1998, 102 (04) :783-791

[5] Membrane-type 1 matrix metalloprotease (MT1-MMP) enables invasive migration of glioma cells in central nervous system white matter [J].

Beliën, ATJ ;

Paganetti, PA ;

Schwab, ME .

JOURNAL OF CELL BIOLOGY, 1999, 144 (02) :373-384

[6] AXOTOMY RESULTS IN DELAYED DEATH AND APOPTOSIS OF RETINAL GANGLION-CELLS IN ADULT-RATS [J].

BERKELAAR, M ;

CLARKE, DB ;

WANG, YC ;

BRAY, GM ;

AGUAYO, AJ .

JOURNAL OF NEUROSCIENCE, 1994, 14 (07) :4368-4374

[7] MORPHOLOGICAL-CHANGES IN OLIGODENDROCYTES IN THE INTACT MOUSE OPTIC-NERVE FOLLOWING INTRAVITREAL INJECTION OF TUMOR-NECROSIS-FACTOR [J].

BUTT, AM ;

JENKINS, HG .

JOURNAL OF NEUROIMMUNOLOGY, 1994, 51 (01) :27-33

[8] Nogo-A is a myelin-associated neurite outgrowth inhibitor and an antigen for monoclonal antibody IN-1 [J].

Chen, MS ;

Huber, AB ;

van der Haar, ME ;

Frank, M ;

Schnell, L ;

Spillmann, AA ;

Christ, F ;

Schwab, ME .

NATURE, 2000, 403 (6768) :434-439

[9] Nogo-A, -B, and -C are found on the cell surface and interact together in many different cell types [J].

Dodd, DA ;

Niederoest, B ;

Bloechlinger, S ;

Dupuis, L ;

Loeffler, JP ;

Schwab, ME .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (13) :12494-12502

[10] Mitogen-Activated Protein Kinase-Signaling Regulates the Ability of Muller Glia to Proliferate and Protect Retinal Neurons Against Excitotoxicity [J].

Fischer, Andy J. ;

Scott, Melissa A. ;

Ritchey, Eric R. ;

Sherwood, Patrick .

GLIA, 2009, 57 (14) :1538-1552

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