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

Cell Death Dis. 2018 Jun 27;9(7):727. doi: 10.1038/s41419-018-0780-x.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing / administration & dosage
  • Antibodies, Neutralizing / pharmacology
  • Down-Regulation / drug effects
  • Electroretinography
  • Gene Expression Regulation / drug effects
  • Intravitreal Injections
  • Male
  • Mice, Inbred C57BL
  • Mice, Knockout
  • N-Methylaspartate / administration & dosage
  • N-Methylaspartate / pharmacology
  • Neuroglia / drug effects
  • Neuroglia / metabolism
  • Neuronal Plasticity* / drug effects
  • Nogo Proteins / metabolism*
  • Recovery of Function* / drug effects
  • Retina / drug effects
  • Retina / injuries*
  • Retina / pathology
  • Retina / physiopathology*
  • Retinal Neurons / drug effects
  • Retinal Neurons / metabolism
  • Vision, Ocular / physiology*


  • Antibodies, Neutralizing
  • Nogo Proteins
  • N-Methylaspartate