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Nogo‐A inhibits vascular regeneration in ischemic retinopathy
Author(s) -
Joly Sandrine,
Dejda Agnieszka,
Rodriguez Léa,
Sapieha Przemyslaw,
Pernet Vincent
Publication year - 2018
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.23462
Subject(s) - biology , angiogenesis , retinal , regeneration (biology) , neuroscience , downregulation and upregulation , retina , neovascularization , microbiology and biotechnology , cancer research , retinopathy , muller glia , immunology , pathology , progenitor cell , medicine , stem cell , endocrinology , biochemistry , gene , diabetes mellitus
Nogo‐A is a potent glial‐derived inhibitor of axon growth in the injured CNS and acts as a negative regulator of developmental angiogenesis by inhibiting vascular endothelial cell migration. However, its function in pathological angiogenesis has never been studied after ischemic injury in the CNS. Using the mouse model of oxygen‐induced retinopathy (OIR) which yields defined zones of retinal ischemia, our goal was to investigate the role of Nogo‐A in vascular regeneration. We demonstrate a marked upregulation of the Nogo‐A receptor sphingosine 1‐phosphate receptor 2 in blood vessels following OIR, while Nogo‐A is abundantly expressed in surrounding glial cells. Acute inhibition of Nogo‐A with function‐blocking antibody 11C7 significantly improved vascular regeneration and consequently prevented pathological pre‐retinal angiogenesis. Ultimately, inhibition of Nogo‐A led to restoration of retinal function as determined by electrophysiological response of retinal cells to light stimulation. Our data suggest that anti‐Nogo‐A antibody may protect neuronal cells from ischemic damage by accelerating blood vessel repair in the CNS. Targeting Nogo‐A by immunotherapy may improve CNS perfusion after vascular injuries.