Suppressing DNMT3a Alleviates the Intrinsic Epigenetic Barrier for Optic Nerve Regeneration and Restores Vision in Adult Mice.

ABSTRACT: The limited regenerative potential of the optic nerve in adult mammals presents a major challenge for restoring vision after optic nerve trauma or disease. The mechanisms of this regenerative failure are not fully understood^1,2. Here, through small-molecule and genetic screening for epigenetic modulators³, we identify DNA methyltransferase 3a (DNMT3a) as a potent inhibitor of axon regeneration in mouse and human retinal explants. Selective suppression of DNMT3a in retinal ganglion cells (RGCs) by gene targeting or delivery of shRNA leads to robust, full-length regeneration of RGC axons through the optic nerve and restoration of vision in adult mice after nerve crush injury. Genome-wide bisulfite and transcriptome profiling in combination with single nucleus RNA-sequen

SUBMITTER: Tai WL 

PROVIDER: S-EPMC10680854 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature