Dynamic structural remodeling of the human visual system prompted by bilateral retinal gene therapy
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 dynamical...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-01-01
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| Series: | Current Research in Neurobiology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2665945X23000177 |
| _version_ | 1827921455168356352 |
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| author | Manzar Ashtari Philip Cook Mikhail Lipin Yinxi Yu Gui-Shuang Ying Albert Maguire Jean Bennett James Gee Hui Zhang |
| author_facet | Manzar Ashtari Philip Cook Mikhail Lipin Yinxi Yu Gui-Shuang Ying Albert Maguire Jean Bennett James Gee Hui Zhang |
| author_sort | Manzar Ashtari |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-13T04:26:48Z |
| format | Article |
| id | doaj.art-53fc31047aaf4981ab917f35a29449d2 |
| institution | Directory Open Access Journal |
| issn | 2665-945X |
| language | English |
| last_indexed | 2024-03-13T04:26:48Z |
| publishDate | 2023-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Current Research in Neurobiology |
| spelling | doaj.art-53fc31047aaf4981ab917f35a29449d22023-06-20T04:20:47ZengElsevierCurrent Research in Neurobiology2665-945X2023-01-014100089Dynamic structural remodeling of the human visual system prompted by bilateral retinal gene therapyManzar Ashtari0Philip Cook1Mikhail Lipin2Yinxi Yu3Gui-Shuang Ying4Albert Maguire5Jean Bennett6James Gee7Hui Zhang8Center for Advanced Retinal and Ocular Therapeutics (CAROT), University of Pennsylvania, Philadelphia, PA, 19104, United States; Department of Ophthalmology, University of Pennsylvania, Philadelphia, PA, 19104, United States; Department of Radiology, University of Pennsylvania, Philadelphia, PA, 19104, United States; Corresponding author. Center for Advanced Retinal and Ocular Therapeutics (CAROT), University of Pennsylvania, Philadelphia, PA, 19104, United States.Department of Radiology, University of Pennsylvania, Philadelphia, PA, 19104, United StatesCenter for Advanced Retinal and Ocular Therapeutics (CAROT), University of Pennsylvania, Philadelphia, PA, 19104, United StatesDepartment of Ophthalmology, University of Pennsylvania, Philadelphia, PA, 19104, United StatesDepartment of Ophthalmology, University of Pennsylvania, Philadelphia, PA, 19104, United StatesCenter for Advanced Retinal and Ocular Therapeutics (CAROT), University of Pennsylvania, Philadelphia, PA, 19104, United States; Department of Ophthalmology, University of Pennsylvania, Philadelphia, PA, 19104, United StatesCenter for Advanced Retinal and Ocular Therapeutics (CAROT), University of Pennsylvania, Philadelphia, PA, 19104, United States; Department of Ophthalmology, University of Pennsylvania, Philadelphia, PA, 19104, United StatesDepartment of Radiology, University of Pennsylvania, Philadelphia, PA, 19104, United StatesCentre for Medical Image Computing, University College London, London, United KingdomThe 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.http://www.sciencedirect.com/science/article/pii/S2665945X23000177Visual systemBrain plasticityMyeline thinningDendritic sproutingRetinal gene therapy |
| spellingShingle | Manzar Ashtari Philip Cook Mikhail Lipin Yinxi Yu Gui-Shuang Ying Albert Maguire Jean Bennett James Gee Hui Zhang Dynamic structural remodeling of the human visual system prompted by bilateral retinal gene therapy Current Research in Neurobiology Visual system Brain plasticity Myeline thinning Dendritic sprouting Retinal gene therapy |
| title | Dynamic structural remodeling of the human visual system prompted by bilateral retinal gene therapy |
| title_full | Dynamic structural remodeling of the human visual system prompted by bilateral retinal gene therapy |
| title_fullStr | Dynamic structural remodeling of the human visual system prompted by bilateral retinal gene therapy |
| title_full_unstemmed | Dynamic structural remodeling of the human visual system prompted by bilateral retinal gene therapy |
| title_short | Dynamic structural remodeling of the human visual system prompted by bilateral retinal gene therapy |
| title_sort | dynamic structural remodeling of the human visual system prompted by bilateral retinal gene therapy |
| topic | Visual system Brain plasticity Myeline thinning Dendritic sprouting Retinal gene therapy |
| url | http://www.sciencedirect.com/science/article/pii/S2665945X23000177 |
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