{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T15:21:42Z","timestamp":1791300102316,"version":"4.1.0"},"reference-count":29,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,1,29]],"date-time":"2021-01-29T00:00:00Z","timestamp":1611878400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Ministry of Science and Technology, Taiwan","award":["MOST 108-2314-B-037-088"],"award-info":[{"award-number":["MOST 108-2314-B-037-088"]}]},{"name":"the Ministry of Science and Technology, Taiwan","award":["MOST 108-2314-B-037-051"],"award-info":[{"award-number":["MOST 108-2314-B-037-051"]}]},{"name":"the Ministry of Science and Technology, Taiwan","award":["MOST 109-2313-B-037-001"],"award-info":[{"award-number":["MOST 109-2313-B-037-001"]}]},{"name":"the Ministry of Science and Technology, Taiwan","award":["109-2314-B-037-069-MY3"],"award-info":[{"award-number":["109-2314-B-037-069-MY3"]}]},{"name":"the Kaohsiung Municipal Siaogang Hospital, Taiwan","award":["KMHK-106-022"],"award-info":[{"award-number":["KMHK-106-022"]}]},{"name":"the Kaohsiung Municipal Siaogang Hospital, Taiwan","award":["KMHK-107-008"],"award-info":[{"award-number":["KMHK-107-008"]}]},{"name":"the Kaohsiung Municipal Siaogang Hospital, Taiwan","award":["KMHK-108-032"],"award-info":[{"award-number":["KMHK-108-032"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Age-related macular degeneration (AMD) is the progressive degeneration of the retinal pigment epithelium (RPE), retina, and choriocapillaris among elderly individuals and is the leading cause of blindness worldwide. Thus, a better understanding of the underlying mechanisms in retinal tissue activated by blue light exposure is important for developing novel treatment and intervention strategies. In this study, blue-light-emitting diodes with a wavelength of 440 nm were applied to RPE cells at a dose of 3.7 \u00b1 0.75 mW\/cm2 for 24 h. ARPE-19 cells were used to investigate the underlying mechanism induced by blue light exposure. A trypan blue exclusion assay was used for the cell viability determination. Flow cytometry was used for apoptosis rate detection and autophagy analysis. An immunofluorescence microscopy analysis was used to investigate cellular oxidative stress and DNA damage using DCFDA fluorescence staining and an anti-\u03b3H2AX antibody. Blue light exposure of zebrafish larvae was established to investigate the effect on retinal tissue development in vivo. To further demonstrate the comprehensive effect of blue light on ARPE-19 cells, next-generation sequencing (NGS) was performed for an ingenuity pathway analysis (IPA) to reveal additional related mechanisms. The results showed that blue light exposure caused a decrease in cell proliferation and an increase in apoptosis in ARPE-19 cells in a time-dependent manner. Oxidative stress increased during the early stage of 2 h of exposure and activated DNA damage in ARPE-19 cells after 8 h. Furthermore, autophagy was activated in response to blue light exposure at 24\u201348 h. The zebrafish larvae model showed the unfavorable effect of blue light in prohibiting retinal tissue development. The RNA-Seq results confirmed that blue light induced cell death and participated in tissue growth inhibition and maturation. The current study reveals the mechanisms by which blue light induces cell death in a time-dependent manner. Moreover, both the in vivo and NGS data uncovered blue light\u2019s effect on retinal tissue development, suggesting that exposing children to blue light could be relatively dangerous. These results could benefit the development of preventive strategies utilizing herbal medicine-based treatments for eye diseases or degeneration in the future.<\/jats:p>","DOI":"10.3390\/ijms22031338","type":"journal-article","created":{"date-parts":[[2021,1,29]],"date-time":"2021-01-29T05:53:43Z","timestamp":1611899623000},"page":"1338","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["The Role of Oxidative Stress and Autophagy in Blue-Light-Induced Damage to the Retinal Pigment Epithelium in Zebrafish In Vitro and In Vivo"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1240-4219","authenticated-orcid":false,"given":"Kai-Chun","family":"Cheng","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Kaohsiung Municipal Siaogang Hospital, Kaohsiung 812, Taiwan"},{"name":"Department of Ophthalmology, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan"},{"name":"Department of Ophthalmology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun-Tzu","family":"Hsu","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Kaohsiung Medical University, Kaohsiung 807, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wangta","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Kaohsiung Medical University, Kaohsiung 807, Taiwan"},{"name":"Center for Cancer Research, Kaohsiung Medical University, Kaohsiung 807, Taiwan"},{"name":"Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huey-Lan","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Bioscience Technology, College of Health Science, Chang Jung Christian University, Tainan 711, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1825-0003","authenticated-orcid":false,"given":"Liang-Yu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen-Xi","family":"He","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Kaohsiung Medical University, Kaohsiung 807, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shwu-Jiuan","family":"Sheu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan"},{"name":"Department of Ophthalmology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuo-Jen","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Kaohsiung Municipal Siaogang Hospital, Kaohsiung 812, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Po-Yen","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2232-9037","authenticated-orcid":false,"given":"Yi-Hsiung","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Kaohsiung Medical University, Kaohsiung 807, Taiwan"},{"name":"Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan"},{"name":"Center for Lipid Biosciences, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan"},{"name":"Lipid Science and Aging Research Center, Kaohsiung Medical University, Kaohsiung 807, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7307-2468","authenticated-orcid":false,"given":"Chien-Chih","family":"Chiu","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Kaohsiung Medical University, Kaohsiung 807, Taiwan"},{"name":"Center for Cancer Research, Kaohsiung Medical University, Kaohsiung 807, Taiwan"},{"name":"Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan"},{"name":"Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung 804, Taiwan"},{"name":"The Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1016\/j.freeradbiomed.2005.01.003","article-title":"Aggregates of oxidized proteins (lipofuscin) induce apoptosis through proteasome inhibition and dysregulation of pro-apoptotic proteins","volume":"38","author":"Powell","year":"2005","journal-title":"Free Radic. 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