Inhibition of Ryanodine Receptor 1 Reduces Endoplasmic Reticulum (ER) Stress and Promotes ER Protein Degradation in Cyclic Nucleotide-Gated Channel Deficiency.
Adv Exp Med Biol
; 1415: 353-358, 2023.
Article
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| MEDLINE
| ID: mdl-37440056
ABSTRACT
The cone photoreceptor cyclic nucleotide-gated (CNG) channel plays a pivotal role in cone phototransduction. Mutations in genes encoding the channel subunits CNGA3 and CNGB3 account for about 80% of all cases of achromatopsia and are associated with progressive cone dystrophies. CNG channel deficiency leads to cellular/endoplasmic reticulum (ER) calcium dysregulation and ER stress-associated cone apoptosis. This work investigated the role of the ER calcium channel ryanodine receptor 1 (Ryr1) in ER stress and cone degeneration in CNG channel deficiency. The AAV-mediated CRISPR/SaCas9 genome editing was used to knock down Ryr1 specifically in cones. CNG channel-deficient mice displayed improved cone survival after subretinal injection of AAV2-SaCas9/gRNA-Ryr1, manifested as increased expression levels of cone proteins M-opsin, S-opsin, and cone arrestin. Knockdown of Ryr1 also led to reduced ER stress and increased expression levels of the ER-associated degradation proteins. This work demonstrates a role of Ryr1 in ER stress and cone degeneration in CNG channel deficiency, and supports strategies targeting ER calcium regulation for cone preservation.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Canal Liberador de Calcio Receptor de Rianodina
/
Canales Catiónicos Regulados por Nucleótidos Cíclicos
Límite:
Animals
Idioma:
En
Revista:
Adv Exp Med Biol
Año:
2023
Tipo del documento:
Article
País de afiliación:
Estados Unidos