Purchase this article with an account.
Julius Baya Mdzomba, Lea Rodriguez, Sandrine Joly, Frederic Bretzner, Vincent Pernet; Nogo-A inactivation promotes visual recovery and plasticity after retinal injury. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5297.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Retinal degeneration is a major cause of blindness in ocular diseases such as glaucoma and in ischemic injuries. The goal of the current study was to determine if neutralizing the glial-derived protein Nogo-A influenced neuronal plasticity and improved visual recovery after retinal lesion.
Excitotoxic injuries were induced at different degrees in the inner retina by injecting 0.02-10 nmoles of N-Methyl-D-Aspartate (NMDA) in the vitreous of adult mice. Control animals received an intravitreal injection of PBS. The effect of neuronal plasticity on vision recovery was studied using KO mice deficient in the myelin-associated protein Nogo-A. Visual functions were tested with the optokinetic reflex (OKR) in awake mice. Retinal and cortical neuron activity changes were monitored by electroretinogram (ERG) and visual evoked potential (VEP) recordings in the eye and in the monocular region of V1, respectively. Retinal ganglion cell (RGC) and amacrine cell survival was assessed by immunofluorescence on retinal histological sections and flat-mounts. Changes in the expression of Nogo-A, Nogo-A receptors, neuronal plasticity-associated proteins were evaluated by qRT-PCR measurements.
In a dose range of 0.02-1 nmole, NMDA induced dose-dependent but reversible OKR loss in WT mice. Strikingly, in Nogo-A KO mice, OKR recovery was much faster and complete than in WT animals. The OKR of the opposite, uninjured eye, also showed a marked increase in sensitivity in KO mice compared with WT. The survival of RGCs was similar in Nogo-A-expressing and KO retinae before and after NMDA injection, and the ERG response did not differ between KO and WT eyes. In contrast, after NMDA injection, the latency of VEP waves was lower in injured KO than in WT brains, suggesting faster visual cortical activation when Nogo-A is deleted. The level of Nogo-A mRNA was not significantly changed after the administration of NMDA while transcripts of growth-associated proteins were transiently upregulated at 24 h Post-injection.
Our results show that the neutralization of Nogo-A promotes vision recovery after NMDA-induced excitotoxic injury in the retina. Therapeutic inhibition of Nogo-A may thus be an effective treatment for retinal pathologies such as glaucoma.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
This PDF is available to Subscribers Only