A genome-wide in vivo CRISPR screen identifies neuroprotective strategies in the mouse and human retina.

Overexpression of UFD1 and UXT prevents photoreceptor degeneration in mouse and human P23H retinitis pigmentosa models, offering promising mutation-agnostic therapies.

• Why it matters: Retinitis pigmentosa is a genetically diverse disease with limited treatment options, necessitating new strategies that can protect retinal cells regardless of specific mutations.
• What they did: A genome-wide in vivo CRISPR knockout screen in mice with the P23H mutation identified genes affecting photoreceptor survival, and subsequent overexpression of UFD1 and UXT validated their neuroprotective effects in both mouse and human retinal explants.
• The result: Augmenting UFD1 and UXT preserved retinal structure and function, demonstrating their potential as broadly applicable therapeutic targets for proteotoxicity-related retinal degeneration.