A genome-wide in vivo CRISPR screen identifies neuroprotective strategies in the mouse and human retina - PubMed
3 hours ago
- #neuroprotection
- #CRISPR screen
- #retinitis pigmentosa
- A genome-wide in vivo CRISPR knockout screen was conducted in mice with the P23H rhodopsin mutation, the most common cause of autosomal dominant retinitis pigmentosa (RP) in the United States.
- The screen identified multiple knockouts that accelerated rod photoreceptor loss and validated top candidates, including UFD1 and UXT.
- Overexpression of UFD1 and UXT preserved rods and cones, maintained retinal function, and improved visual behaviors in mice.
- A human P23H RP model was developed using adult retinal explants, replicating key disease features.
- UFD1 and UXT augmentation also prevented photoreceptor degeneration in the human P23H retinal model.
- The study establishes a pipeline for identifying and testing neuroprotective genes in mouse and human RP models, highlighting UFD1 and UXT as mutation-agnostic therapeutic strategies against proteotoxicity.