June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Effects of Retinal Gene Therapy on Auditory-Visual Cross Modal Plasticity: Does Re-Established Vision Kick Auditory Activity out of the Occipital Lobe?
Author Affiliations & Notes
  • Aimee E Willett
    Center for Advanced Retinal and Ocular Therapeutics (CAROT), University of Pennsylvania, Philadelphia, Pennsylvania, United States
  • Mani Mahmoudian
    Center for Advanced Retinal and Ocular Therapeutics (CAROT), University of Pennsylvania, Philadelphia, Pennsylvania, United States
  • Gloria J. Young
    Center for Advanced Retinal and Ocular Therapeutics (CAROT), University of Pennsylvania, Philadelphia, Pennsylvania, United States
  • Albert M Maguire
    Center for Advanced Retinal and Ocular Therapeutics (CAROT), University of Pennsylvania, Philadelphia, Pennsylvania, United States
    Department of Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania, United States
  • Jean Bennett
    Center for Advanced Retinal and Ocular Therapeutics (CAROT), University of Pennsylvania, Philadelphia, Pennsylvania, United States
    Department of Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania, United States
  • Manzar Ashtari
    Center for Advanced Retinal and Ocular Therapeutics (CAROT), University of Pennsylvania, Philadelphia, Pennsylvania, United States
    Department of Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania, United States
  • Footnotes
    Commercial Relationships   Aimee Willett, None; Mani Mahmoudian, None; Gloria J. Young, None; Albert Maguire, US Patent number 8147823 (P); Jean Bennett, Avalanche Technologies (C), Gensight Biologics (C), Sanofi-Aventis (C), US Patent number 8147823 (P); Manzar Ashtari, None
  • Footnotes
    Support  This study was supported by R01EY025287-01A1, R21EY020662 from the National Eye Institute. This study was also funded in part by the Foundation Fighting Blindness–sponsored CHOP-PENN Pediatric Center for Retinal Degenerations, Clinical Translational Science Award NIH/NCRR UL1-RR-024134, 1R01EY019014-01A2, Research to Prevent Blindness, the Paul and Evanina Mackall Foundation Trust at Scheie Eye Institute and the F. M. Kirby Foundation.
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 4680. doi:
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      Aimee E Willett, Mani Mahmoudian, Gloria J. Young, Albert M Maguire, Jean Bennett, Manzar Ashtari; Effects of Retinal Gene Therapy on Auditory-Visual Cross Modal Plasticity: Does Re-Established Vision Kick Auditory Activity out of the Occipital Lobe?. Invest. Ophthalmol. Vis. Sci. 2017;58(8):4680.

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

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Abstract

Purpose : We used functional magnetic resonance imaging (fMRI) to explore the fate of auditory-driven cross modal (CM) activity within the visual cortex in a group of Leber’s Congenital Amaurosis (LCA) patients after sight restoration through retinal gene therapy (GT).

Methods : Participants consisted of 8 LCA patients and 8 normal-sighted controls. LCA patients were administered retinal GT in their worse seeing eye as part of a Phase-I clinical trial and subsequently received GT in their contralateral eye in a second follow-on clinical trial. [1] Auditory (tonal interval) and visual (checkerboard) task fMRI activations were recorded an average of 3 months before and 3 years after GT re-administration. fMRI group general linear model analysis was conducted using BrainVoyagerQX. Pearson correlations between auditory and visual task occipital cortex activations were also performed.

[1] Bennett J, Wellman J, Marshall KA, et al. Safety and durability of effect of contralateral-eye administration of AAV2 gene therapy in patients with childhood-onset blindness caused by RPE65 mutations: a follow-on phase 1 trial. Lancet 2016;388(10045):661-72.

Results : Group results from the auditory task show significant CM visual cortex activity before and after vision restoration in LCA patients. An increase in visual cortex activation area is observable 3 years after GT. Controls show no visual cortex activation during the auditory task. Results from visual task stimulation of the left and right eyes after GT show significant and widespread occipital lobe activations. Correlations show strong trends and significant relationships between areas of visually vs. auditory stimulated visual cortex activation areas at the 3-year time point. Activity of the right hemisphere has the strongest correlation between both tasks (p<0.03).

Conclusions : Our results show persistence of CM auditory activity within the visual cortex in a group of LCA subjects 3 years after successful vision restoration. Significant correlations between the auditory and visual task activations within the primary visual cortex 3 years after vision restoration showed a strong relationship between CM plasticity and response to vision. This may indicate a relationship between the strengthening of the visual pathway as a result of GT and increase in CM activation.

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

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