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
em En
| 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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Canal de Liberação de Cálcio do Receptor de Rianodina
/
Canais de Cátion Regulados por Nucleotídeos Cíclicos
Limite:
Animals
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article