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. This GIRK-channel-based strategy offers a promising method to preserve high-quality vision in RCD patients, regardless of their specific genetic mutation.
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BibTeX
@article{simon2026reactivating,
title = {{Reactivating the phototransduction cascade with a mutation agnostic gene therapy preserves vision in rod-cone dystrophies}},
author = {Cardillia-Joe Simon and Hanen Khabou and Antoine Chaffiol and Marco Rucli and Marion Finzi and Nat Norberg and Anaïs Grimaud and Brix Mücher and Mélissa Desrosiers and Serge Sancho and Vera Lucia Bonilha and Kate Grieve and Jens Duebel and Michel Paques and Serge Picaud and José Alain Sahel and Isabelle Audo and Stefan Herlitze and Deniz Dalkara},
journal = {iScience},
year = {2026},
month = oct,
doi = {10.1016/j.isci.2025.112106},
url = {https://hal.science/hal-05797284v1},
note = {CC BY},
}
RIS
TY - JOUR
TI - Reactivating the phototransduction cascade with a mutation agnostic gene therapy preserves vision in rod-cone dystrophies
AU - Cardillia-Joe Simon
AU - Hanen Khabou
AU - Antoine Chaffiol
AU - Marco Rucli
AU - Marion Finzi
AU - Nat Norberg
AU - Anaïs Grimaud
AU - Brix Mücher
AU - Mélissa Desrosiers
AU - Serge Sancho
AU - Vera Lucia Bonilha
AU - Kate Grieve
AU - Jens Duebel
AU - Michel Paques
AU - Serge Picaud
AU - José Alain Sahel
AU - Isabelle Audo
AU - Stefan Herlitze
AU - Deniz Dalkara
PY - 2026
DA - 2026/10/13
JO - iScience
DO - 10.1016/j.isci.2025.112106
UR - https://hal.science/hal-05797284v1
AB - 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. This GIRK-channel-based strategy offers a promising method to preserve high-quality vision in RCD patients, regardless of their specific genetic mutation.
SN - 2589-0042
ER -