Published in

American Society for Clinical Investigation, Journal of Clinical Investigation, 6(121), p. 2160-2168, 2011

DOI: 10.1172/jci57377

American Society for Clinical Investigation, Journal of Clinical Investigation, 7(121), p. 2945-2945

DOI: 10.1172/jci59208

Links

Tools

Export citation

Search in Google Scholar

The human visual cortex responds to gene therapy–mediated recovery of retinal function

Journal article published in 2011 by Manzar Ashtari, Laura L. Cyckowski, Justin F. Monroe, Kathleen A. Marshall, Daniel C. Chung, Alberto Auricchio ORCID, Francesca Simonelli, Bart P. Leroy, Albert M. Maguire, Kenneth S. Shindler, Jean Bennett
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

Full text: Download

Red circle
Preprint: archiving forbidden
Red circle
Postprint: archiving forbidden
Green circle
Published version: archiving allowed
Upload
Policy details
Data provided by SHERPA/RoMEO

Abstract

Leber congenital amaurosis (LCA) is a rare degenerative eye disease, linked to mutations in at least 14 genes. A recent gene therapy trial in patients with LCA2, who have mutations in RPE65, demonstrated that subretinal injection of an acieno-associated virus (AAV) carrying the normal cDNA of that gene (AAV2-hRPE65v2) could markedly improve vision. However, it remains unclear how the visual cortex responds to recovery of retinal function after prolonged sensory deprivation. Here, 3 of the gene therapy trial subjects, treated at ages 8, 9, and 35 years, underwent functional MRI within 2 years of unilateral injection of AAV2-hRPE6Sv2. All subjects showed increased cortical activation in response to high- and medium-contrast stimuli after exposure to the treated compared with the untreated eye. Furthermore, we observed a correlation between the visual field maps and the distribution of cortical activations for the treated eyes. These data suggest that despite severe and long-term visual impairment, treated LCA2 patients have intact and responsive visual pathways. In addition, these data suggest that gene therapy resulted in not only sustained and improved visual ability, but also enhanced contrast sensitivity.