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Dynamic structural remodeling of the human visual system prompted by bilateral retinal gene therapy

Ashtari, Manzar; Cook, Philip; Lipin, Mikhail; Yu, Yinxi; Ying, Gui-Shuang; Maguire, Albert; Bennett, Jean; ... Zhang, Hui; + view all (2023) Dynamic structural remodeling of the human visual system prompted by bilateral retinal gene therapy. Current Research in Neurobiology , 4 , Article 100089. 10.1016/j.crneur.2023.100089. Green open access

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Abstract

The impact of changes in visual input on neuronal circuitry is complex and much of our knowledge on human brain plasticity of the visual systems comes from animal studies. Reinstating vision in a group of patients with low vision through retinal gene therapy creates a unique opportunity to dynamically study the underlying process responsible for brain plasticity. Historically, increases in the axonal myelination of the visual pathway has been the biomarker for brain plasticity. Here, we demonstrate that to reach the long-term effects of myelination increase, the human brain may undergo demyelination as part of a plasticity process. The maximum change in dendritic arborization of the primary visual cortex and the neurite density along the geniculostriate tracks occurred at three months (3MO) post intervention, in line with timing for the peak changes in postnatal synaptogenesis within the visual cortex reported in animal studies. The maximum change at 3MO for both the gray and white matter significantly correlated with patients' clinical responses to light stimulations called full field sensitivity threshold (FST). Our results shed a new light on the underlying process of brain plasticity by challenging the concept of increase myelination being the hallmark of brain plasticity and instead reinforcing the idea of signal speed optimization as a dynamic process for brain plasticity.

Type: Article
Title: Dynamic structural remodeling of the human visual system prompted by bilateral retinal gene therapy
Location: Netherlands
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.crneur.2023.100089
Publisher version: https://doi.org/10.1016/j.crneur.2023.100089
Language: English
Additional information: © 2023 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/bync-nd/4.0/).
Keywords: Brain plasticity, Dendritic sprouting, Myeline thinning, Retinal gene therapy, Visual system
UCL classification: UCL
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Computer Science
URI: https://discovery.ucl.ac.uk/id/eprint/10172910
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