Advertisement
The human visual cortex responds to gene therapy–mediated recovery of retinal function
Manzar Ashtari,1 Laura L. Cyckowski,1 Justin F. Monroe,1 Kathleen A. Marshall,2 Daniel C. Chung,2,3 Alberto Auricchio,4,5 Francesca Simonelli,4,6 Bart P. Leroy,7 Albert M. Maguire,2,3 Kenneth S. Shindler,3 and Jean Bennett2,3
1Department of Radiology and 2Center for Cellular and Molecular Therapeutics, Children’s Hospital of Philadelphia (CHOP), Philadelphia, Pennsylvania, USA. 3F.M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA. 4Telethon Institute of Genetics and Medicine (TIGEM) and 5Medical Genetics, Department of Pediatrics, “Federico II University,” Naples, Italy. 6Second University of Naples, Naples, Italy. 7Department of Ophthalmology and Center for Medical Genetics, Ghent University and Ghent University Hospital, Ghent, Belgium.
Find articles by Ashtari, M. in: JCI | PubMed | Google Scholar
1Department of Radiology and 2Center for Cellular and Molecular Therapeutics, Children’s Hospital of Philadelphia (CHOP), Philadelphia, Pennsylvania, USA. 3F.M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA. 4Telethon Institute of Genetics and Medicine (TIGEM) and 5Medical Genetics, Department of Pediatrics, “Federico II University,” Naples, Italy. 6Second University of Naples, Naples, Italy. 7Department of Ophthalmology and Center for Medical Genetics, Ghent University and Ghent University Hospital, Ghent, Belgium.
Find articles by Cyckowski, L. in: JCI | PubMed | Google Scholar
1Department of Radiology and 2Center for Cellular and Molecular Therapeutics, Children’s Hospital of Philadelphia (CHOP), Philadelphia, Pennsylvania, USA. 3F.M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA. 4Telethon Institute of Genetics and Medicine (TIGEM) and 5Medical Genetics, Department of Pediatrics, “Federico II University,” Naples, Italy. 6Second University of Naples, Naples, Italy. 7Department of Ophthalmology and Center for Medical Genetics, Ghent University and Ghent University Hospital, Ghent, Belgium.
Find articles by Monroe, J. in: JCI | PubMed | Google Scholar
1Department of Radiology and 2Center for Cellular and Molecular Therapeutics, Children’s Hospital of Philadelphia (CHOP), Philadelphia, Pennsylvania, USA. 3F.M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA. 4Telethon Institute of Genetics and Medicine (TIGEM) and 5Medical Genetics, Department of Pediatrics, “Federico II University,” Naples, Italy. 6Second University of Naples, Naples, Italy. 7Department of Ophthalmology and Center for Medical Genetics, Ghent University and Ghent University Hospital, Ghent, Belgium.
Find articles by Marshall, K. in: JCI | PubMed | Google Scholar
1Department of Radiology and 2Center for Cellular and Molecular Therapeutics, Children’s Hospital of Philadelphia (CHOP), Philadelphia, Pennsylvania, USA. 3F.M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA. 4Telethon Institute of Genetics and Medicine (TIGEM) and 5Medical Genetics, Department of Pediatrics, “Federico II University,” Naples, Italy. 6Second University of Naples, Naples, Italy. 7Department of Ophthalmology and Center for Medical Genetics, Ghent University and Ghent University Hospital, Ghent, Belgium.
Find articles by Chung, D. in: JCI | PubMed | Google Scholar
1Department of Radiology and 2Center for Cellular and Molecular Therapeutics, Children’s Hospital of Philadelphia (CHOP), Philadelphia, Pennsylvania, USA. 3F.M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA. 4Telethon Institute of Genetics and Medicine (TIGEM) and 5Medical Genetics, Department of Pediatrics, “Federico II University,” Naples, Italy. 6Second University of Naples, Naples, Italy. 7Department of Ophthalmology and Center for Medical Genetics, Ghent University and Ghent University Hospital, Ghent, Belgium.
Find articles by Auricchio, A. in: JCI | PubMed | Google Scholar
1Department of Radiology and 2Center for Cellular and Molecular Therapeutics, Children’s Hospital of Philadelphia (CHOP), Philadelphia, Pennsylvania, USA. 3F.M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA. 4Telethon Institute of Genetics and Medicine (TIGEM) and 5Medical Genetics, Department of Pediatrics, “Federico II University,” Naples, Italy. 6Second University of Naples, Naples, Italy. 7Department of Ophthalmology and Center for Medical Genetics, Ghent University and Ghent University Hospital, Ghent, Belgium.
Find articles by Simonelli, F. in: JCI | PubMed | Google Scholar
1Department of Radiology and 2Center for Cellular and Molecular Therapeutics, Children’s Hospital of Philadelphia (CHOP), Philadelphia, Pennsylvania, USA. 3F.M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA. 4Telethon Institute of Genetics and Medicine (TIGEM) and 5Medical Genetics, Department of Pediatrics, “Federico II University,” Naples, Italy. 6Second University of Naples, Naples, Italy. 7Department of Ophthalmology and Center for Medical Genetics, Ghent University and Ghent University Hospital, Ghent, Belgium.
Find articles by Leroy, B. in: JCI | PubMed | Google Scholar
1Department of Radiology and 2Center for Cellular and Molecular Therapeutics, Children’s Hospital of Philadelphia (CHOP), Philadelphia, Pennsylvania, USA. 3F.M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA. 4Telethon Institute of Genetics and Medicine (TIGEM) and 5Medical Genetics, Department of Pediatrics, “Federico II University,” Naples, Italy. 6Second University of Naples, Naples, Italy. 7Department of Ophthalmology and Center for Medical Genetics, Ghent University and Ghent University Hospital, Ghent, Belgium.
Find articles by Maguire, A. in: JCI | PubMed | Google Scholar
1Department of Radiology and 2Center for Cellular and Molecular Therapeutics, Children’s Hospital of Philadelphia (CHOP), Philadelphia, Pennsylvania, USA. 3F.M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA. 4Telethon Institute of Genetics and Medicine (TIGEM) and 5Medical Genetics, Department of Pediatrics, “Federico II University,” Naples, Italy. 6Second University of Naples, Naples, Italy. 7Department of Ophthalmology and Center for Medical Genetics, Ghent University and Ghent University Hospital, Ghent, Belgium.
Find articles by Shindler, K. in: JCI | PubMed | Google Scholar
1Department of Radiology and 2Center for Cellular and Molecular Therapeutics, Children’s Hospital of Philadelphia (CHOP), Philadelphia, Pennsylvania, USA. 3F.M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA. 4Telethon Institute of Genetics and Medicine (TIGEM) and 5Medical Genetics, Department of Pediatrics, “Federico II University,” Naples, Italy. 6Second University of Naples, Naples, Italy. 7Department of Ophthalmology and Center for Medical Genetics, Ghent University and Ghent University Hospital, Ghent, Belgium.
Find articles by Bennett, J. in: JCI | PubMed | Google Scholar
Published July 1, 2011 - More info
J Clin Invest. 2011;121(7):2945–2945. https://doi.org/10.1172/JCI59208.
© 2011 The American Society for Clinical Investigation
Related article:
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 adeno-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-hRPE65v2. 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.
Authors
Manzar Ashtari, Laura L. Cyckowski, Justin F. Monroe, Kathleen A. Marshall, Daniel C. Chung, Alberto Auricchio, Francesca Simonelli, Bart P. Leroy, Albert M. Maguire, Kenneth S. Shindler, Jean Bennett
Original citation: J. Clin. Invest. 2011;121(6):2160–2168. doi:10.1172/JCI57377.
Citation for this corrigendum: J. Clin. Invest. 2011;121(7):2945. doi:10.1172/JCI59208.
In the author list, Francesca Simonelli’s affiliation was incorrect. The correct information appears above.
The authors regret the error.
Copyright © 2022 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)