Plasticity of the human visual system after retinal gene therapy in patients with Leber’s congenital amaurosis

Details

• Alternative Title:
  Sci Transl Med
• Personal Author:
  Ashtari, Manzar ; Zhang, Hui ; Cook, Philip A. ; Cyckowski, Laura L. ; Shindler, Kenneth S. ; Marshall, Kathleen A. ; Aravand, Puya ; Vossough, Arastoo ; Gee, James C. ; Maguire, Albert M. ; Baker, Chris I. ; Bennett, Jean
• Description:
  Much of our knowledge of the mechanisms underlying plasticity in the visual cortex in response to visual impairment, vision restoration, and environmental interactions comes from animal studies. We evaluated human brain plasticity in a group of patients with Leber's congenital amaurosis (LCA), who regained vision through gene therapy. Using non-invasive multimodal neuroimaging methods, we demonstrated that reversing blindness with gene therapy promoted long-term structural plasticity in the visual pathways emanating from the treated retina of LCA patients. The data revealed improvements and normalization along the visual fibers corresponding to the site of retinal injection of the gene therapy vector carrying the therapeutic gene in the treated eye compared to the visual pathway for the untreated eye of LCA patients. After gene therapy, the primary visual pathways (for example, geniculostriate fibers) in the treated retina were similar to those of sighted control subjects, whereas the primary visual pathways of the untreated retina continued to deteriorate. Our results suggest that visual experience, enhanced by gene therapy, may be responsible for the reorganization and maturation of synaptic connectivity in the visual pathways of the treated eye in LCA patients. The interactions between the eye and the brain enabled improved and sustained long-term visual function in patients with LCA after gene therapy.
• Subjects:
  Adolescent Adult Anisotropy Article Case-Control Studies Child Diffusion Tensor Imaging Female Genetic Therapy Genetic Vectors Humans Leber Congenital Amaurosis Magnetic Resonance Imaging Male Middle Aged Neuroimaging Neuronal Plasticity Retina Vision, Ocular Visual Cortex Young Adult

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• Source:
  Sci Transl Med. 7(296):296ra110
• Pubmed ID:
  26180100
• Pubmed Central ID:
  PMC4617524
• Document Type:
  Journal Article
• Funding:
  R21EY020662/EY/NEI NIH HHS/United States ; 1R24EY019861/EY/NEI NIH HHS/United States ; R24 EY019861/EY/NEI NIH HHS/United States ; Intramural NIH HHS/United States ; DP1 EY023177/EY/NEI NIH HHS/United States ; P30 EY001583/EY/NEI NIH HHS/United States ; R21 EY020662/EY/NEI NIH HHS/United States ; 8DP1EY023177/DP/NCCDPHP CDC HHS/United States
• Volume:
  7
• Issue:
  296
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:e5eb38ef1788058312eb52e7abb765dd66f4ca7ea78f490d06f3fc58307372b2
• Download URL:
  https://stacks.cdc.gov/view/cdc/35293/cdc_35293_DS1.pdf
• File Type:
  [PDF - 854.46 KB ]