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A small molecule compound that inhibits blue light-induced retinal damage via activation of autophagy
- Title
- A small molecule compound that inhibits blue light-induced retinal damage via activation of autophagy
- Authors
- Shin Y.C.; Lee S.; Jin H.L.; Fei X.; Kang S.W.; Seo S.-Y.; Jeong K.W.
- Ewha Authors
- 강상원
- SCOPUS Author ID
- 강상원
- Issue Date
- 2023
- Journal Title
- Biochemical Pharmacology
- ISSN
- 0006-2952
- Citation
- Biochemical Pharmacology vol. 211
- Publisher
- Elsevier Inc.
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- Abstract
- Dry age-related macular degeneration (AMD) is a type of disease that causes visual impairment due to changes in the macula located in the center of the retina. The accumulation of drusen under the retina is also a characteristic of dry AMD. In this study, we identified a compound (JS-017) that can potentially degrade N-retinylidene-N-retinylethanolamine (A2E), one of the components of lipofuscin, using fluorescence-based screening, which measures A2E degradation in human retinal pigment epithelial cells. JS-017 effectively degraded A2E in ARPE-19 cells and consequently suppressed the activation of the NF-κB signaling pathway and expression of inflammatory and apoptosis genes induced by blue light (BL). Mechanistically, JS-017 induced LC3-II formation and improved autophagic flux in ARPE-19 cells. Additionally, the A2E degradation activity of JS-017 was found to be decreased in autophagy-related 5 protein-depleted ARPE-19 cells, suggesting that autophagy was required for A2E degradation mediated by JS-017. Finally, JS-017 exhibited an improvement in BL-induced retinal damage measured through fundus examination in an in vivo retinal degeneration mouse model. The thickness of the outer nuclear layer and inner/external segments, which was decreased upon exposure to BL irradiation, was also restored upon JS-017 treatment. Altogether, we demonstrated that JS-017 protected human retinal pigment epithelium (RPE) cells from A2E and BL-induced damage by degrading A2E via the activation of autophagy. The results suggest the feasibility of a novel A2E-degrading small molecule as a therapeutic agent for retinal degenerative diseases. © 2023 Elsevier Inc.
- DOI
- 10.1016/j.bcp.2023.115534
- Appears in Collections:
- 자연과학대학 > 생명과학전공 > Journal papers
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