June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
The combined administration of the two products encoded by the nucleoredoxin-like-I gene stabilizes vision in a mouse model of retinitis pigmentosa
Author Affiliations & Notes
  • Thierry D Leveillard
    Institut De La Vision, Paris, France
  • Emmanuelle Clerin
    Institut De La Vision, Paris, France
  • Najate Maamri Maamri
    Institut De La Vision, Paris, France
  • ying yang
    Institut De La Vision, Paris, France
  • Geraldine Millet-Puel
    Institut De La Vision, Paris, France
  • Frédéric Blond
    Institut De La Vision, Paris, France
  • Deniz Dalkara
    Institut De La Vision, Paris, France
  • Alain VAN DORSSELAER
    Univertsity of Strasbourg, Strasbourg, France
  • José Alain sahel
    Institut De La Vision, Paris, France
  • Footnotes
    Commercial Relationships   Thierry Leveillard, None; Emmanuelle Clerin, None; Najate Maamri, None; ying yang, None; Geraldine Millet-Puel, None; Frédéric Blond, None; Deniz Dalkara, None; Alain VAN DORSSELAER, None; José Alain sahel, None
  • Footnotes
    Support  Inserm, UPMC, ANR, Labex LIFESENSE, Fondtaion Fighting Blindness
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 1576. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to Subscribers Only
      Sign In or Create an Account ×
    • Get Citation

      Thierry D Leveillard, Emmanuelle Clerin, Najate Maamri Maamri, ying yang, Geraldine Millet-Puel, Frédéric Blond, Deniz Dalkara, Alain VAN DORSSELAER, José Alain sahel; The combined administration of the two products encoded by the nucleoredoxin-like-I gene stabilizes vision in a mouse model of retinitis pigmentosa. Invest. Ophthalmol. Vis. Sci. 2017;58(8):1576.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : The nucleoredoxin-like 1 gene (NXNL1) encodes by alternative splicing for the trophic factor RdCVF that stimulates aerobic glycolysis in cones by interaction with its cell surface receptor basigin-1 that is linked to the glucose transporter GLUT1. RdCVF accelerates glucose uptake by cones to sustain cone outer segment renewal. RdCVF prevents secondary cone degeneration in recessive and dominant animal models of retinitis pigmentosa. The second product of the NXNL1 gene, the thioredoxin RdCVFL protects the cones against hyperoxia. We evaluated the effect of a combined administration of the two products encoded by the gene on visual acuity of a recessive model of retinitis pigmentosa, the rd10 mouse.

Methods : An adeno-associated viral vector encoding for both products of the NXNL1 gene: the thioredoxin RdCVFL and the truncated thioredoxin RdCVF was administrated by subretinal injection to the rd10 mouse. The kinetics of the loss of visual acuity was recorded by optokinetic nystagmus testing. Cone density was then measured using e-conome.

Results : The loss of visual acuity was statistically significantly retarded after injection of AAV-RdCVF-RdCVFL that an AAV vector targets retinal pigmented epithelial cells and cones and very significantly considering the medical objective. Cone density was higher in animals treated with the combination of the two transgenes. Thus, the administration of RdCVF or RdCVFL prevents visual loss in the rd10 mouse using a non cell- and a cell-autonomous mechanism respectively.

Conclusions : The results demonstrate that this metabolic and redox treatment will likely be successful in preserving central vision in patients suffering of retinitis pigmentosa independently of causative mutations.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

×
×

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.

×