Reactivating the phototransduction cascade with a mutation agnostic gene therapy preserves vision in rod-cone dystrophies.

ABSTRACT: Rod-cone dystrophy (RCD) comprises genetic conditions where rod photoreceptor degeneration leads to cone loss, causing progressive vision loss. We investigated the phototransduction cascade in degenerating cones using two RCD mouse models and found that opsin and arrestin expression continues in the cell body during outer segment degeneration. Based on this observation, we explored reactivating cones through G-protein-coupled inwardly rectifying K (GIRK) channel expression. Using adeno-associated viral delivery of GIRK channels, we achieved improved visual function in both mouse models. Additionally, we examined human tissue from late-stage RCD patients and confirmed the presence of cone opsin and cone arrestin expression, supporting the potential therapeutic application of this approach.

SUBMITTER: Simon CJ 

PROVIDER: S-EPMC11960651 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature