Reactivating the phototransduction cascade with a mutation agnostic gene therapy preserves vision in rod-cone dystrophies Article Swipe
Cardillia-Joe Simon
,
Hanen Khabou
,
Antoine Chaffiol
,
Marco Rucli
,
Marion Finzi
,
Nat Norberg
,
Anaïs Grimaud
,
Brix Mücher
,
Mélissa Desrosiers
,
Serge Sancho
,
Vera L. Bonilha
,
Kate Grieve
,
Jens Duebel
,
Michel Pâques
,
Serge Picaud
,
José‐Alain Sahel
,
Isabelle Audo
,
Stefan Herlitze
,
Deniz Dalkara
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1016/j.isci.2025.112106
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1016/j.isci.2025.112106
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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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1016/j.isci.2025.112106
- OA Status
- gold
- References
- 56
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4407928849
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4407928849Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1016/j.isci.2025.112106Digital Object Identifier
- Title
-
Reactivating the phototransduction cascade with a mutation agnostic gene therapy preserves vision in rod-cone dystrophiesWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2025Year of publication
- Publication date
-
2025-02-25Full publication date if available
- Authors
-
Cardillia-Joe Simon, Hanen Khabou, Antoine Chaffiol, Marco Rucli, Marion Finzi, Nat Norberg, Anaïs Grimaud, Brix Mücher, Mélissa Desrosiers, Serge Sancho, Vera L. Bonilha, Kate Grieve, Jens Duebel, Michel Pâques, Serge Picaud, José‐Alain Sahel, Isabelle Audo, Stefan Herlitze, Deniz DalkaraList of authors in order
- Landing page
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https://doi.org/10.1016/j.isci.2025.112106Publisher landing page
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YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://doi.org/10.1016/j.isci.2025.112106Direct OA link when available
- Concepts
-
Visual phototransduction, Genetic enhancement, Cone (formal languages), Cascade, Gene, Biology, Neuroscience, Genetics, Retina, Chemistry, Computer science, Chromatography, AlgorithmTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
0Total citation count in OpenAlex
- References (count)
-
56Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.confirmed | 89 |
| abstract_inverted_index.continues | 38 |
| abstract_inverted_index.dystrophy | 1 |
| abstract_inverted_index.mutation. | 126 |
| abstract_inverted_index.patients, | 120 |
| abstract_inverted_index.potential | 101 |
| abstract_inverted_index.promising | 112 |
| abstract_inverted_index.conditions | 5 |
| abstract_inverted_index.expression | 37 |
| abstract_inverted_index.late-stage | 85 |
| abstract_inverted_index.rectifying | 58 |
| abstract_inverted_index.regardless | 121 |
| abstract_inverted_index.supporting | 99 |
| abstract_inverted_index.application | 103 |
| abstract_inverted_index.expression, | 98 |
| abstract_inverted_index.expression. | 62 |
| abstract_inverted_index.progressive | 15 |
| abstract_inverted_index.therapeutic | 102 |
| abstract_inverted_index.degenerating | 24 |
| abstract_inverted_index.degeneration | 9 |
| abstract_inverted_index.high-quality | 116 |
| abstract_inverted_index.investigated | 19 |
| abstract_inverted_index.observation, | 50 |
| abstract_inverted_index.reactivating | 53 |
| abstract_inverted_index.Additionally, | 79 |
| abstract_inverted_index.degeneration. | 46 |
| abstract_inverted_index.photoreceptor | 8 |
| abstract_inverted_index.adeno-associated | 64 |
| abstract_inverted_index.G-protein-coupled | 56 |
| abstract_inverted_index.phototransduction | 21 |
| abstract_inverted_index.GIRK-channel-based | 108 |
| cited_by_percentile_year | |
| countries_distinct_count | 4 |
| institutions_distinct_count | 19 |
| citation_normalized_percentile.value | 0.0569463 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |