{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T03:10:33Z","timestamp":1782789033600,"version":"3.54.5"},"reference-count":75,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,4,9]],"date-time":"2023-04-09T00:00:00Z","timestamp":1680998400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Catania","award":["RC2022-N4"],"award-info":[{"award-number":["RC2022-N4"]}]},{"name":"Italian Ministry of Health Research Program","award":["RC2022-N4"],"award-info":[{"award-number":["RC2022-N4"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Age-related macular degeneration (AMD) has been described as a progressive eye disease characterized by irreversible impairment of central vision, and unfortunately, an effective treatment is still not available. It is well-known that amyloid-beta (A\u03b2) peptide is one of the major culprits in causing neurodegeneration in Alzheimer\u2019s disease (AD). The extracellular accumulation of this peptide has also been found in drusen which lies under the retinal pigment epithelium (RPE) and represents one of the early signs of AMD pathology. A\u03b2 aggregates, especially in the form of oligomers, are able to induce pro-oxidant (oxidative stress) and pro-inflammatory phenomena in RPE cells. ARPE-19 is a spontaneously arising human RPE cell line validated for drug discovery processes in AMD. In the present study, we employed ARPE-19 treated with A\u03b2 oligomers, representing an in vitro model of AMD. We used a combination of methods, including ATPlite, quantitative real-time PCR, immunocytochemistry, as well as a fluorescent probe for reactive oxygen species to investigate the molecular alterations induced by A\u03b2 oligomers. In particular, we found that A\u03b2 exposure decreased the cell viability of ARPE-19 cells which was paralleled by increased inflammation (increased expression of pro-inflammatory mediators) and oxidative stress (increased expression of NADPH oxidase and ROS production) along with the destruction of ZO-1 tight junction protein. Once the damage was clarified, we investigated the therapeutic potential of carnosine, an endogenous dipeptide that is known to be reduced in AMD patients. Our findings demonstrate that carnosine was able to counteract most of the molecular alterations induced by the challenge of ARPE-19 with A\u03b2 oligomers. These new findings obtained with ARPE-19 cells challenged with A\u03b21-42 oligomers, along with the well-demonstrated multimodal mechanism of action of carnosine both in vitro and in vivo, able to prevent and\/or counteract the dysfunctions elicited by A\u03b2 oligomers, substantiate the neuroprotective potential of this dipeptide in the context of AMD pathology.<\/jats:p>","DOI":"10.3390\/molecules28083324","type":"journal-article","created":{"date-parts":[[2023,4,10]],"date-time":"2023-04-10T03:24:18Z","timestamp":1681097058000},"page":"3324","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Carnosine Counteracts the Molecular Alterations A\u03b2 Oligomers-Induced in Human Retinal Pigment Epithelial Cells"],"prefix":"10.3390","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1571-5327","authenticated-orcid":false,"given":"Giuseppe","family":"Caruso","sequence":"first","affiliation":[{"name":"Department of Drug and Health Sciences, University of Catania, 95125 Catania, Italy"},{"name":"Unit of Neuropharmacology and Translational Neurosciences, Oasi Research Institute-IRCCS, 94018 Troina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia G.","family":"Fresta","sequence":"additional","affiliation":[{"name":"Department of Drug and Health Sciences, University of Catania, 95125 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9279-0171","authenticated-orcid":false,"given":"Annamaria","family":"Fidilio","sequence":"additional","affiliation":[{"name":"Unit of Neuropharmacology and Translational Neurosciences, Oasi Research Institute-IRCCS, 94018 Troina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9825-2104","authenticated-orcid":false,"given":"Francesca","family":"Lazzara","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2451-1158","authenticated-orcid":false,"given":"Nicol\u00f2","family":"Musso","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy"},{"name":"Bio-Nanotech Research and Innovation Tower (BRIT), University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7050-1375","authenticated-orcid":false,"given":"Vincenzo","family":"Cardaci","sequence":"additional","affiliation":[{"name":"Vita-Salute San Raffaele University, 20132 Milano, Italy"},{"name":"Scuola Superiore di Catania, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filippo","family":"Drago","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filippo","family":"Caraci","sequence":"additional","affiliation":[{"name":"Department of Drug and Health Sciences, University of Catania, 95125 Catania, Italy"},{"name":"Unit of Neuropharmacology and Translational Neurosciences, Oasi Research Institute-IRCCS, 94018 Troina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Bucolo","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy"},{"name":"Center for Research in Ocular Pharmacology-CERFO, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.17219\/acem\/27093","article-title":"The dry form of age-related macular degeneration (amd): The current concepts of pathogenesis and prospects for treatment","volume":"24","author":"Pilecka","year":"2015","journal-title":"Adv. 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