A small molecule compound that inhibits blue light-induced retinal damage via activation of autophagy
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Shin, Chae Young | - |
dc.contributor.author | Lee, Sanha | - |
dc.contributor.author | Jin, Hong Lan | - |
dc.contributor.author | Fei, Xiang | - |
dc.contributor.author | Kang, Sang Won | - |
dc.contributor.author | Seo, Seung-Yong | - |
dc.contributor.author | Jeong, Kwang Won | - |
dc.date.accessioned | 2023-05-16T00:41:05Z | - |
dc.date.available | 2023-05-16T00:41:05Z | - |
dc.date.created | 2023-05-15 | - |
dc.date.issued | 2023-05 | - |
dc.identifier.issn | 0006-2952 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/87677 | - |
dc.description.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-ret-inylidene-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-?B 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 exami-nation 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 ther-apeutic agent for retinal degenerative diseases. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | PERGAMON-ELSEVIER SCIENCE LTD | - |
dc.relation.isPartOf | BIOCHEMICAL PHARMACOLOGY | - |
dc.title | A small molecule compound that inhibits blue light-induced retinal damage via activation of autophagy | - |
dc.type | Article | - |
dc.type.rims | ART | - |
dc.description.journalClass | 1 | - |
dc.identifier.wosid | 000979023400001 | - |
dc.identifier.doi | 10.1016/j.bcp.2023.115534 | - |
dc.identifier.bibliographicCitation | BIOCHEMICAL PHARMACOLOGY, v.211 | - |
dc.description.isOpenAccess | N | - |
dc.identifier.scopusid | 2-s2.0-85151890271 | - |
dc.citation.title | BIOCHEMICAL PHARMACOLOGY | - |
dc.citation.volume | 211 | - |
dc.contributor.affiliatedAuthor | Shin, Chae Young | - |
dc.contributor.affiliatedAuthor | Lee, Sanha | - |
dc.contributor.affiliatedAuthor | Fei, Xiang | - |
dc.contributor.affiliatedAuthor | Seo, Seung-Yong | - |
dc.contributor.affiliatedAuthor | Jeong, Kwang Won | - |
dc.type.docType | Article | - |
dc.subject.keywordPlus | VACCINIUM-ULIGINOSUM L. | - |
dc.subject.keywordPlus | MACULAR DEGENERATION | - |
dc.subject.keywordPlus | A2E | - |
dc.subject.keywordPlus | PATHOGENESIS | - |
dc.subject.keywordPlus | LUTEIN | - |
dc.subject.keywordPlus | CELLS | - |
dc.subject.keywordPlus | AMD | - |
dc.relation.journalResearchArea | Pharmacology & Pharmacy | - |
dc.relation.journalWebOfScienceCategory | Pharmacology & Pharmacy | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.
1342, Seongnam-daero, Sujeong-gu, Seongnam-si, Gyeonggi-do, Republic of Korea(13120)031-750-5114
COPYRIGHT 2020 Gachon University All Rights Reserved.
Certain data included herein are derived from the © Web of Science of Clarivate Analytics. All rights reserved.
You may not copy or re-distribute this material in whole or in part without the prior written consent of Clarivate Analytics.