Restoring Vision in Adult Amblyopia by Enhancing Plasticity Through Deletion of the Transcriptional Repressor REST

Overview

Journal iScience

Publisher Cell Press

Date 2024 Apr 9

PMID 38591011

Authors

Dmytro Shmal

Giulia Mantero

Thomas Floss

Fabio Benfenati

Jose Fernando Maya-Vetencourt

Affiliations

Soon will be listed here.

Abstract

Visual cortical plasticity is high during early life, but gradually decreases with development. This is due to the Otx2-driven maturation of intracortical inhibition that parallels the condensation of extracellular matrix components into perineuronal nets mainly around parvalbumin-positive GABAergic neurons. Repressor Element 1 Silencing Transcription (REST) epigenetically controls the expression of a plethora of neuron-specific genes. We demonstrate that the conditional knockout of REST in the primary visual cortex of adult mice induces a shift of ocular dominance after short-term monocular deprivation and promotes the recovery of vision in long-term deprived animals after reverse suture. These phenomena paralleled a reduction of perineuronal net density and increased expression of REST target genes, but not of the homeoprotein Otx2 in the visual cortex contralateral to the deprived eye. This shows that REST regulates adult visual cortical plasticity and is a potential therapeutic target to restore vision in adult amblyopia by enhancing V1 plasticity.

Citing Articles

Interactions between excitatory neurons and parvalbumin interneurons in V1 underlie neural mechanisms of amblyopia and visual stimulation treatment.

Huang Y, Liu Z, Zhan Z, Zhang X, Gao L, Wang M Commun Biol. 2024; 7(1):1564.

PMID: 39587348 PMC: 11589704. DOI: 10.1038/s42003-024-07296-x.

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