{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T19:13:31Z","timestamp":1768677211500,"version":"3.49.0"},"reference-count":32,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2020,1,6]],"date-time":"2020-01-06T00:00:00Z","timestamp":1578268800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"2017 Genentech\/ARVO AMD Translational Research Fellowship","award":["NA"],"award-info":[{"award-number":["NA"]}]},{"name":"RPB (Research to Prevent Blindness) pilot research grant","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"DOI":"10.13039\/100000997","name":"Arnold and Mabel Beckman Foundation","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100000997","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016547","name":"UCI School of Medicine","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100016547","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002806","name":"Discovery Eye Foundation","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100002806","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Guenther Foundation","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"DOI":"10.13039\/100008226","name":"Beckman Initiative for Macular Research","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100008226","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Polly and Michael Smith Foundation","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"name":"Max Factor Family Foundation","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"name":"Iris and B. Gerald Cantor Foundation","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"name":"research was supported in part by an unrestricted grant from RPB","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"name":"SN is a recipient of the 2017 Genentech\/ARVO AMD Translational Research Fellowship and the 2016 RPB pilot research grant.","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Resveratrol is a phytoalexin, stilbenoid compound with antioxidant properties attributable to its bioactive trans-resveratrol content. This study characterized the effects of over-the-counter (OTC) resveratrol nutritional supplements and a HPLC-purified resveratrol formulation, in human transmitochondrial age-related macular degeneration (AMD) retinal pigment epithelial (RPE) patient cell lines. These cell lines, which were created by fusing blood platelets obtained from dry and wet AMD patients with mitochondria-deficient (Rho0) ARPE-19 cells, had identical nuclei (derived from ARPE-19 cells) but different mitochondria that were derived from AMD patients. After resveratrol treatment, the levels of cell viability and reactive oxygen species production were measured. Results demonstrated that treatment with different resveratrol formulations improved cell viability and decreased reactive oxygen species generation in each AMD patient cell line. Although further studies are required to establish the cytoprotective potential of resveratrol under different physiological conditions, this novel study established the positive effects of OTC resveratrol supplements in macular degeneration patient cybrid cell lines in vitro.<\/jats:p>","DOI":"10.3390\/nu12010159","type":"journal-article","created":{"date-parts":[[2020,1,6]],"date-time":"2020-01-06T10:34:46Z","timestamp":1578306886000},"page":"159","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Role of Resveratrol in Transmitochondrial AMD RPE Cells"],"prefix":"10.3390","volume":"12","author":[{"given":"Sonali","family":"Nashine","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Gavin Herbert Eye Institute, University of California Irvine, Irvine, CA 92697, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony B.","family":"Nesburn","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Gavin Herbert Eye Institute, University of California Irvine, Irvine, CA 92697, USA"},{"name":"Cedars-Sinai Medical Center, Los Angeles, CA 92697, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Baruch D.","family":"Kuppermann","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Gavin Herbert Eye Institute, University of California Irvine, Irvine, CA 92697, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Cristina","family":"Kenney","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Gavin Herbert Eye Institute, University of California Irvine, Irvine, CA 92697, USA"},{"name":"Department of Pathology and Laboratory Medicine, University of California Irvine, Irvine, CA 92697, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,1,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.medici.2016.03.003","article-title":"Multiplicity of effects and health benefits of resveratrol","volume":"52","year":"2016","journal-title":"Medicina"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Chang, X., Heene, E., Qiao, F., and Nick, P. (2011). The phytoalexin resveratrol regulates the initiation of hypersensitive cell death in Vitis cell. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0026405"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1186\/1752-153X-5-88","article-title":"Trans-, cis-, and dihydro-resveratrol: A comparative study","volume":"5","author":"Anisimova","year":"2011","journal-title":"Chem. Cent. J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1111\/j.1749-6632.2010.05842.x","article-title":"Bioavailability of resveratrol","volume":"1215","author":"Walle","year":"2011","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/S0009-9120(02)00397-1","article-title":"Absorption of three wine-related polyphenols in three different matrices by healthy subjects","volume":"36","author":"Goldberg","year":"2003","journal-title":"Clin. Biochem."},{"key":"ref_6","first-page":"S3","article-title":"Optimizing Anti-VEGF Treatment Outcomes for Patients with Neovascular Age-Related Macular Degeneration","volume":"24","author":"Wykoff","year":"2018","journal-title":"J. Manag. Care Spec. Pharm."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Lan\u00e7on, A., Frazzi, R., and Latruffe, N. (2016). Anti-Oxidant, Anti-Inflammatory and Anti-Angiogenic Properties of Resveratrol in Ocular Diseases. Molecules, 21.","DOI":"10.3390\/molecules21030304"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e2951","DOI":"10.1038\/cddis.2017.348","article-title":"Humanin G (HNG) protects age-related macular degeneration (AMD) transmitochondrial ARPE-19 cybrids from mitochondrial and cellular damage","volume":"8","author":"Nashine","year":"2017","journal-title":"Cell Death Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"15175","DOI":"10.1038\/s41598-018-33290-5","article-title":"Characterizing the protective effects of SHLP2, a mitochondrial-derived peptide, in macular degeneration","volume":"8","author":"Nashine","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Nashine, S., Nesburn, A.B., Kuppermann, B.D., and Kenney, M.C. (2019). Age-related macular degeneration (AMD) mitochondria modulate epigenetic mechanisms in retinal pigment epithelial cells. Exp. Eye Res., 189.","DOI":"10.1016\/j.exer.2019.107701"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Nashine, S., Chwa, M., Kazemian, M., Thaker, K., Lu, S., Nesburn, A., Kuppermann, B.D., and Kenney, M.C. (2016). Differential Expression of Complement Markers in Normal and AMD Transmitochondrial Cybrids. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0159828"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.18632\/aging.101820","article-title":"Nutraceutical effects of Emblica officinalis in age-related macular degeneration","volume":"11","author":"Nashine","year":"2019","journal-title":"Aging"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"6691","DOI":"10.18632\/aging.102179","article-title":"PU-91 drug rescues human age-related macular degeneration RPE cells; implications for AMD therapeutics","volume":"11","author":"Nashine","year":"2019","journal-title":"Aging"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1887","DOI":"10.2174\/092986708785132951","article-title":"Trans-resveratrol: A magical elixir of eternal youth?","volume":"15","author":"Orallo","year":"2008","journal-title":"Curr. Med. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Andres, S., Pevny, S., Ziegenhagen, R., Bakhiya, N., Sch\u00e4fer, B., Hirsch-Ernst, K.I., and Lampen, A. (2018). Safety Aspects of the Use of Quercetin as a Dietary Supplement. Mol. Nutr. Food Res., 62.","DOI":"10.1002\/mnfr.201700447"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1650","DOI":"10.1080\/02713683.2017.1344713","article-title":"Resveratrol Ameliorates Retinal Ischemia\/Reperfusion Injury in C57BL\/6J Mice via Downregulation of Caspase-3","volume":"42","author":"Seong","year":"2017","journal-title":"Curr. Eye Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3879","DOI":"10.1167\/iovs.18-23806","article-title":"Resveratrol Delays Retinal Ganglion Cell Loss and Attenuates Gliosis-Related Inflammation from Ischemia-Reperfusion Injury","volume":"59","author":"Luo","year":"2018","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1969","DOI":"10.1016\/j.neurobiolaging.2014.12.021","article-title":"Protection of injured retinal ganglion cell dendrites and unfolded protein response resolution after long-term dietary resveratrol","volume":"36","author":"Lindsey","year":"2015","journal-title":"Neurobiol. Aging"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"943","DOI":"10.7150\/ijms.19391","article-title":"Effects of Hypobaric Hypoxia on Rat Retina and Protective Response of Resveratrol to the Stress","volume":"14","author":"Xin","year":"2017","journal-title":"Int. J. Med. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Means, J.C., Gerdes, B.C., and Koulen, P. (2017). Distinct Mechanisms Underlying Resveratrol-Mediated Protection from Types of Cellular Stress in C6 Glioma Cells. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18071521"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1016\/S0891-5849(02)00982-6","article-title":"Photosensitized oxidation of 2\u2032,7\u2032-dichlorofluorescin: Singlet oxygen does not contribute to the formation of fluorescent oxidation product 2\u2032,7\u2032-dichlorofluorescein","volume":"33","author":"Bilski","year":"2002","journal-title":"Free Radic. Biol. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1152\/physrev.00026.2013","article-title":"Mitochondrial reactive oxygen species (ROS) and ROS-induced ROS release","volume":"94","author":"Zorov","year":"2014","journal-title":"Physiol. Rev."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1089\/152308603770310202","article-title":"The free radical theory of aging","volume":"5","author":"Harman","year":"2003","journal-title":"Antioxid. Redox Signal."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"10","DOI":"10.2174\/1874609810801010010","article-title":"The mitochondrial free radical theory of aging: A critical view","volume":"1","author":"Sanz","year":"2008","journal-title":"Curr. Aging Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"R453","DOI":"10.1016\/j.cub.2014.03.034","article-title":"ROS function in redox signaling and oxidative stress","volume":"24","author":"Schieber","year":"2014","journal-title":"Curr. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1186\/s12937-016-0186-5","article-title":"The importance of antioxidants which play the role in cellular response against oxidative\/nitrosative stress: Current state","volume":"15","author":"Kurutas","year":"2016","journal-title":"Nutr. J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"5025","DOI":"10.1021\/jo9007095","article-title":"Radical-scavenging activity and mechanism of resveratrol-oriented analogues: Influence of the solvent, radical, and substitution","volume":"74","author":"Shang","year":"2009","journal-title":"J. Org. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.phrs.2005.08.002","article-title":"Upregulation of endogenous antioxidants and phase 2 enzymes by the red wine polyphenol, resveratrol in cultured aortic smooth muscle cells leads to cytoprotection against oxidative and electrophilic stress","volume":"53","author":"Li","year":"2006","journal-title":"Pharmacol. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.diabres.2016.12.005","article-title":"Resveratrol ameliorates hyperglycemia-induced renal tubular oxidative stress damage via modulating the SIRT1\/FOXO3a pathway","volume":"126","author":"Wang","year":"2017","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3117","DOI":"10.18632\/aging.101966","article-title":"Exploration of age-related mitochondrial dysfunction and the anti-aging effects of resveratrol in zebrafish retina","volume":"11","author":"Wang","year":"2019","journal-title":"Aging"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"9003","DOI":"10.1158\/0008-5472.CAN-10-2364","article-title":"Repeat dose study of the cancer chemopreventive agent resveratrol in healthy volunteers: Safety, pharmacokinetics, and effect on the insulin-like growth factor axis","volume":"70","author":"Brown","year":"2010","journal-title":"Cancer Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1419","DOI":"10.1158\/1940-6207.CAPR-11-0148","article-title":"Phase I randomized, double-blind pilot study of micronized resveratrol (SRT501) in patients with hepatic metastases\u2014Safety, pharmacokinetics, and pharmacodynamics","volume":"4","author":"Howells","year":"2011","journal-title":"Cancer Prev. Res."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/12\/1\/159\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:18:57Z","timestamp":1760361537000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/12\/1\/159"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,6]]},"references-count":32,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,1]]}},"alternative-id":["nu12010159"],"URL":"https:\/\/doi.org\/10.3390\/nu12010159","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,6]]}}}