Nogo-A inactivation improves visual plasticity and recovery after retinal injury.

TitleNogo-A inactivation improves visual plasticity and recovery after retinal injury.
Publication TypeJournal Article
Year of Publication2018
AuteursMdzomba, JBaya, Jordi, N, Rodriguez, L, Joly, S, Bretzner, F, Pernet, V
JournalCell Death Dis
Date Published2018 Jun 27

Myelin-associated proteins such as Nogo-A are major inhibitors of neuronal plasticity that contribute to permanent neurological impairments in the injured CNS. In the present study, we investigated the influence of Nogo-A on visual recovery after retinal injuries in mice. Different doses of N-methyl-D-aspartate (NMDA) were injected in the vitreous of the left eye to induce retinal neuron death. The visual function was monitored using the optokinetic response (OKR) as a behavior test, and electroretinogram (ERG) and local field potential (LFP) recordings allowed to assess changes in retinal and cortical neuron activity, respectively. Longitudinal OKR follow-ups revealed reversible visual deficits after injection of NMDA ≤ 1 nmole in the left eye and concomitant functional improvement in the contralateral visual pathway of the right eye that was let intact. Irreversible OKR loss observed with NMDA ≥ 2 nmol was correlated with massive retinal cell death and important ERG response decline. Strikingly, the OKR mediated by injured and intact eye stimulation was markedly improved in Nogo-A KO mice compared with WT animals, suggesting that the inactivation of Nogo-A promotes visual recovery and plasticity. Moreover, OKR improvement was associated with shorter latency of the N2 wave of Nogo-A KO LFPs relative to WT animals. Strikingly, intravitreal injection of anti-Nogo-A antibody (11C7) in the injured eye exerted positive effects on cortical LFPs. This study presents the intrinsic ability of the visual system to recover from NMDA-induced retinal injury and its limitations. Nogo-A neutralization may promote visual recovery in retinal diseases such as glaucoma.

Alternate JournalCell Death Dis
PubMed ID29950598
PubMed Central IDPMC6021388
Grant List34204 / / Canada Foundation for Innovation (Fondation canadienne pour l'innovation) /
30633 / / Fonds de Recherche du Québec - Santé (Fonds de la recherche en sante du Quebec) /