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

• Published in: Current research in neurobiology 2023-01, Vol.4, p.100089-100089, Article 100089
• Main Authors: Ashtari, Manzar, Cook, Philip, Lipin, Mikhail, Yu, Yinxi, Ying, Gui-Shuang, Maguire, Albert, Bennett, Jean, Gee, James, Zhang, Hui
• Format: Article
• Language: English
• Subjects: Brain plasticity; Dendritic sprouting; Myeline thinning; Retinal gene therapy; Visual system
• ISSN: 2665-945X; 2665-945X
• DOI: 10.1016/j.crneur.2023.100089

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. [Display omitted] •Vision restoration promotes high degrees of brain plasticity in both gray and white matter.•Here we demonstrate axons go under a demyelination stage before their remyelination process.•Maximum brain changes for both gray and white matter occurred at 3 months after retinal intervention.•The gray and white matter changes at 3 months post intervention significantly correlates with patients' clinical responses.•Results suggest that patients may benefit from a carefully designed rehabilitation program.