All-Trans Retinoic Acid Attenuates Blue Light-Induced Apoptosis of Retinal Photoreceptors by Upregulating MKP-1 Expression.
Mol Neurobiol
; 58(8): 4157-4168, 2021 Aug.
Article
em En
| MEDLINE
| ID: mdl-33950345
ABSTRACT
The study investigated the antiapoptotic effects of all-trans retinoic acid (RA) on retinal degeneration caused by exposure to blue light. Sprague-Dawley rats received intraperitoneal injections of RA and, if necessary, the mitogen-activated protein kinase phosphotase-1(MKP-1) inhibitor, (E)-2-benzylidene-3-(cyclohexylamino)-2, 3-dihydro-1H-inden-1-one (BCI), or the retinoic acid receptor (RAR) antagonist, AGN 193109. Retinal damage was induced by 24 h of continuous exposure to blue light. Haematoxylin and eosin staining and electroretinography were performed to measure retinal thickness and retinal function before and at 3 days and 7 days after light exposure. The retinal protein expression levels of phosphorylated c-Jun N-terminal kinase (JNK), phosphorylated nuclear factor-κB, MKP-1, Bim, Bax, and cleaved caspase-3 were also measured. Terminal-deoxynucleotidyl-transferase-mediated deoxyuridine triphosphate-biotin nick end labelling (TUNEL) staining and immunofluorescent staining of cleaved caspase-3 were also performed to evaluate photoreceptor apoptosis. The administration of RA significantly mitigated retinal dysfunction and the decrease in the outer nuclear layer (ONL) thickness at 3 days and 7 days after light exposure. RA also reduced the percentage of TUNEL-positive nuclei in the ONL and cleaved caspase-3 immunofluorescence intensity at 3 days after light exposure. Light exposure increased the retinal expression of proapoptotic proteins (Bim, Bax, and cleaved caspase-3), which was attenuated by RA. Moreover, RA enhanced the expression of MKP-1 and inhibited the phosphorylation of JNK, which were attenuated by the inhibition of RAR. The inhibitory effects of RA on blue light-induced photoreceptor apoptosis were abrogated by the MKP-1inhibitor. Our results indicate that RA alleviates photoreceptor loss following blue light exposure, at least partly, by the MKP-1/JNK pathway, which may serve as a therapeutic target for relieving retinal degeneration.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tretinoína
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Regulação para Cima
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Apoptose
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Células Fotorreceptoras de Vertebrados
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Fosfatase 1 de Especificidade Dupla
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Luz
Limite:
Animals
Idioma:
En
Revista:
Mol Neurobiol
Assunto da revista:
BIOLOGIA MOLECULAR
/
NEUROLOGIA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
China