July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Neuronal Nogo-A upregulation promotes retinal ganglion cell axon dystrophy: a new mechanism underlying glaucoma-induced optic nerve axonopathy?
Author Affiliations & Notes
  • Léa Rodriguez
    Ophthalmology, Universite Laval - CHUL, Quebec, Quebec, Canada
  • Sandrine Joly
    Ophthalmology, Universite Laval - CHUL, Quebec, Quebec, Canada
  • Julius Baya Mdzomba
    Ophthalmology, Universite Laval - CHUL, Quebec, Quebec, Canada
  • Deniz Dalkara
    Institut de la vision, Paris, France
  • Vincent Pernet
    Ophthalmology, Universite Laval - CHUL, Quebec, Quebec, Canada
  • Footnotes
    Commercial Relationships   Léa Rodriguez, None; Sandrine Joly, None; Julius Mdzomba, None; Deniz Dalkara, None; Vincent Pernet, None
  • Footnotes
    Support  FRQS, grant # 30633, the Velux Stiftung (grant # 988), CFI, project # 34204
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 657. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Léa Rodriguez, Sandrine Joly, Julius Baya Mdzomba, Deniz Dalkara, Vincent Pernet; Neuronal Nogo-A upregulation promotes retinal ganglion cell axon dystrophy: a new mechanism underlying glaucoma-induced optic nerve axonopathy?. Invest. Ophthalmol. Vis. Sci. 2019;60(9):657.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Purpose : Glaucoma, the second cause of blindness worldwide, is characterized by optic nerve degeneration and retinal ganglion cell (RGC) death. Here, we hypothesized that optic nerve axon dystrophy is mediated by Nogo-A upregulation in RGCs prior to neuronal death. Nogo-A is a well-known glial-derived inhibitor of neuronal plasticity but its function in neurodegenerative processes is unclear.

Methods : Nogo-A expression changes were followed in a mouse model of hypertensive glaucoma induced by microbead injection in the anterior chamber of adult C57BL/6J mice, a well-accepted method to induce trabecular meshwork occlusion. Ocular hypertension was controlled using a tonometer. Nogo-A expression and RGC survival were analyzed by immunofluorescence on whole retinae. To determine if Nogo-A expression is sufficient to cause axonal dystrophy and neuronal death, adeno-associated virus (AAV) serotype 2.2 containing Nogo-A cDNA was intravitreally injected. After two months of infection, retinal function was monitored by electroretinography (ERG) and RGC survival was quantified. Nogo-A overexpression and RGC morphology were evaluated in infected and uninjected retinae.

Results : After 4 weeks of increased intraocular pressure, RGC survival was decreased by ~20% (3368 ± 145 cells; mean ± S.E.M, n=4 mice) compared to contralateral retinae (4022 ± 88 cells; mean ± S.E.M, n=4 mice). Interestingly, no functional alteration was observed by ERG when Nogo-A was upregulated in the RGCs of hypertensive retinae. AAV2.2-induced Nogo-A was located in axonal swellings at the surface of infected retinae, in contrast to control retinae exhibiting Nogo-A in RGC somata. Nogo-A overexpression was also correlated with an increase in the cell surface of RGCs. Surprisingly, this phenotype was similar to that obtained with the overactivation of the mTOR pathway following PTEN silencing with AAV2.2-shRNA-PTEN. This later vector had the ability to enhance the level of Nogo-A in RGCs, suggesting a possible control of Nogo-A expression by mTOR signalling in large RGCs.

Conclusions : Our results suggest that the increase of Nogo-A in glaucoma may contribute to RGC soma hypertrophy and early axonopathy in the optic nerve. This process may depend on mTOR signalling activation.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×