Nogo-A inhibits vascular regeneration in ischemic retinopathy.

Abstract:

: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.

journal_name

Glia

journal_title

Glia

authors

Joly S,Dejda A,Rodriguez L,Sapieha P,Pernet V

doi

10.1002/glia.23462

subject

Has Abstract

pub_date

2018-10-01 00:00:00

pages

2079-2093

issue

10

eissn

0894-1491

issn

1098-1136

journal_volume

66

pub_type

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