Nogo‐A inhibits vascular regeneration in ischemic retinopathy. Issue 10 (27th July 2018)

• Record Type: Journal Article
• Authors: Joly, Sandrine; Dejda, Agnieszka; Rodriguez, Léa; Sapieha, Przemyslaw; Pernet, Vincent
• Is Part Of: Glia. Volume 66:Issue 10(2018)
• Page Start: 2079
• Page End: 2093
• Publication Date: 2018-07-27
• Subjects: glia -- immunotherapy -- Nogo‐A -- oxygen‐induced retinopathy -- vascular repair; Neuroglia -- Periodicals; Neurology -- Periodicals; 611.0188
• DOI: 10.1002/glia.23462
• Languages: English
• ISSNs: 0894-1491

Abstract

Main Points: This study reveals a new inhibitory function for the glial protein Nogo‐A in pathological angiogenesis. Acute blockade of Nogo‐A is a potent strategy to promote vascular regeneration and neuronal recovery after retinal ischemia. The effects of Nogo‐A neutralizing antibody on vascular regeneration are independent of VEGF signaling. 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.