{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T22:53:01Z","timestamp":1790635981057,"version":"4.1.0"},"reference-count":35,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2020,1,27]],"date-time":"2020-01-27T00:00:00Z","timestamp":1580083200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Purpose: To investigate the mechanism by which resveratrol acts upon retinal pigment epithelial (RPE) cells and to characterize its effect upon autophagy, survival, and inflammation, with consequent implications to treatment for age-related macular degeneration (AMD). Methods: Cultured ARPE-19 cells were exposed to 10 and 50 \u03bcM resveratrol. Cell survival\/death was determined by annexin-FITC\/propidium iodide using flow cytometry, while autophagy was studied by detecting autophagic vacuoles formation (acridine orange and transmission electron microscopy), as well as LC3II\/I ratio and p62 expression by Western blot. In addition, time-lapse confocal microscopy of a pDENDRA-LC3 expression vector was performed to detect autophagy in transfected ARPE-19 cells under the different treatment conditions. Inhibition of proteasomal and autophagy-lysosomal fusion was carried out by MG-132 and chloroquine, respectively, while induction of autophagy was achieved by rapamycin treatment. Detection of secreted cytokines by ARPE-19 cells using Human XL Cytokine Array was performed under oxidative stress (H2O2) and resveratrol treatments, respectively. Results: Resveratrol induced autophagy in ARPE-19 cells as determined by augmented presence of autophagic vacuoles, increased LC3II\/I ratio and decreased p62 expression, as well as time-lapse confocal microscopy using pDENDRA-LC3 expression vector. Resveratrol acted similarly to proteasomal inhibition and downstream of mammalian target of rapamycin (mTOR), since upstream inhibition of autophagy by 3-methyladenine could not inhibit autophagy in ARPE-19 cells. Co-treatmeant by rapamycin and\/or proteasome inhibition showed no additive effect upon autophagy induction. ARPE-19 cells treated by resveratrol showed lower cell death rate compared to untreated controls. Resveratrol induced a specific anti-inflammatory response in ARPE-19 cells. Conclusions: Resveratrol can induce autophagy, pro-survival, and anti-inflammatory stimuli in ARPE-19 cells, properties which could be plausible to formulate future treatment modalities for AMD.<\/jats:p>","DOI":"10.3390\/ijms21030813","type":"journal-article","created":{"date-parts":[[2020,1,27]],"date-time":"2020-01-27T11:41:57Z","timestamp":1580125317000},"page":"813","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":59,"title":["Resveratrol as Inducer of Autophagy, Pro-Survival, and Anti-Inflammatory Stimuli in Cultured Human RPE Cells"],"prefix":"10.3390","volume":"21","author":[{"given":"Natasha","family":"Josifovska","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Center for Eye Research, Oslo University Hospital and University of Oslo, 0450 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R\u00e9ka","family":"Albert","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Faculty of Medicine, University of Szeged, 6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rich\u00e1rd","family":"Nagymih\u00e1ly","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Center for Eye Research, Oslo University Hospital and University of Oslo, 0450 Oslo, Norway"},{"name":"Department of Ophthalmology, Faculty of Medicine, University of Szeged, 6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lyubomyr","family":"Lytvynchuk","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Faculty of Medicine, University of Szeged, 6720 Szeged, Hungary"},{"name":"Department of Ophthalmology, Justus-Liebig-University Giessen, Eye Clinic, University Hospital Giessen, 35390 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morten C.","family":"Moe","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Center for Eye Research, Oslo University Hospital and University of Oslo, 0450 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Kaarniranta","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland and Kuopio University Hospital, 70210 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9518-2155","authenticated-orcid":false,"given":"Zolt\u00e1n J.","family":"Ver\u00e9b","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Faculty of Medicine, University of Szeged, 6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Goran","family":"Petrovski","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Center for Eye Research, Oslo University Hospital and University of Oslo, 0450 Oslo, Norway"},{"name":"Department of Ophthalmology, Faculty of Medicine, University of Szeged, 6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,1,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5293258","DOI":"10.1155\/2017\/5293258","article-title":"Cellular Senescence in Age-Related Macular Degeneration: Can Autophagy and DNA Damage Response Play a Role?","volume":"2017","author":"Blasiak","year":"2017","journal-title":"Oxid. 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