December 2010
Volume 10, Issue 15
Free
OSA Fall Vision Meeting Abstract  |   December 2010
Restoration of rod function following gene therapy in patients with mutations in the gene encoding the RPE65 protein required for recycling all-trans-retinal to 11-cis-retinal
Author Affiliations
  • Andrew Stockman
    UCL Institute of Ophthalmology, London, UK
  • Caterina Ripamonti
    UCL Institute of Ophthalmology, London, UK
  • G. Bruce Henning
    UCL Institute of Ophthalmology, London, UK
  • Scott J. Robbie
    UCL Institute of Ophthalmology, London, UK
  • Anthony T. Moore
    UCL Institute of Ophthalmology, London, UK
  • James W. Bainbridge
    UCL Institute of Ophthalmology, London, UK
  • Robin R. Ali
    UCL Institute of Ophthalmology, London, UK
Journal of Vision December 2010, Vol.10, 59. doi:10.1167/10.15.59
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Andrew Stockman, Caterina Ripamonti, G. Bruce Henning, Scott J. Robbie, Anthony T. Moore, James W. Bainbridge, Robin R. Ali; Restoration of rod function following gene therapy in patients with mutations in the gene encoding the RPE65 protein required for recycling all-trans-retinal to 11-cis-retinal. Journal of Vision 2010;10(15):59. doi: 10.1167/10.15.59.

      Download citation file:


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

      ×
  • Supplements
Abstract

Rod visual function can be confirmed unequivocally by demonstrating that visual performance measured as a function of wavelength has a rod spectral sensitivity. We have used this test to assess retinal function in some of the patients with early onset severe retinal dystrophy enrolled in an ongoing phase-I/II dose-escalation clinical trial of gene therapy for RPE65 deficiency. The therapy involves subretinal delivery of a recombinant adeno-associated viral vector expressing RPE65. The particular visual performance task used was the threshold detection of 1-Hz flicker following 40 minutes of dark adaptation. The flickering target was 3.55-deg in diameter presented 10-deg in the superior retina (close to the treatment site). We made spectral sensitivity measurements prior to gene therapy and then at 2-monthly intervals following gene therapy in the last five patients enrolled in the trial (to date). Prior to gene therapy, no clear evidence of rod function was found in the spectral sensitivity measurements. The flicker spectral sensitivity functions in all patients were cone-like and similar to those found during the cone plateau after an intense bleach. After gene therapy, however, substantial improvements in flicker sensitivity were found in the first two patients tested. One patient showed a 1000-fold improvement in dark-adapted flicker sensitivity at 500 nm, 4 months after treatment and the second a 100-fold improvement, 6 months after treatment. In both cases, the spectral sensitivity became clearly rod-like, indicative of restored rod function. To date, the other patients have not shown an improvement using this test. The trial is ongoing.

Acknowledgments
NIHR Biomedical Research Centre for Ophthalmology, London. 
Fight for Sight. 
×
×

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.

×