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Crocetin inhibits choroidal neovascularization in both in vitro and in vivo models.
- Source :
-
Experimental eye research [Exp Eye Res] 2024 Jan; Vol. 238, pp. 109751. Date of Electronic Publication: 2023 Dec 13. - Publication Year :
- 2024
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Abstract
- Choroidal neovascularization (CNV) is the primary pathogenic process underlying wet age-related macular degeneration, leading to severe vision loss. Despite current anti-vascular endothelial growth factor (VEGF) therapies, several limitations persist. Crocetin, a major bioactive constituent of saffron, exhibits multiple pharmacological activities, yet its role and mechanism in CNV remain unclear. Here, we investigated the potential effects of crocetin on CNV using in vitro and in vivo models. In human umbilical vein endothelial cells, crocetin demonstrated inhibition of VEGF-induced cell proliferation, migration, and tube formation in vitro, as assessed by CCK-8 and EdU assays, transwell and scratch assays, and tube formation analysis. Additionally, crocetin suppressed choroidal sprouting in ex vivo experiments. In the human retinal pigment epithelium (RPE) cell line ARPE-19, crocetin attenuated cobalt chloride-induced hypoxic cell injury, as evidenced by CCK-8 assay. As evaluated by quantitative PCR and Western blot assay, it also reduced hypoxia-induced expression of VEGF and hypoxia-inducible factor 1α (HIF-1α), while enhancing zonula occludens-1 expression. In a laser-induced CNV mouse model, intravitreal administration of crocetin significantly reduced CNV size and suppressed elevated expressions of VEGF, HIF-1α, TNFα, IL-1β, and IL-6. Moreover, crocetin treatment attenuated the elevation of phospho-S6 in laser-induced CNV and hypoxia-induced RPE cells, suggesting its potential anti-angiogenic effects through antagonizing the mechanistic target of rapamycin complex 1 (mTORC1) signaling. Our findings indicate that crocetin may hold promise as an effective drug for the prevention and treatment of CNV.<br /> (Copyright © 2023. Published by Elsevier Ltd.)
- Subjects :
- Mice
Animals
Humans
Vascular Endothelial Growth Factor A metabolism
Sincalide metabolism
Hypoxia metabolism
Disease Models, Animal
Retinal Pigment Epithelium metabolism
Endothelial Cells metabolism
Choroidal Neovascularization drug therapy
Choroidal Neovascularization prevention & control
Choroidal Neovascularization metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1096-0007
- Volume :
- 238
- Database :
- MEDLINE
- Journal :
- Experimental eye research
- Publication Type :
- Academic Journal
- Accession number :
- 38097101
- Full Text :
- https://doi.org/10.1016/j.exer.2023.109751