{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T02:56:17Z","timestamp":1785207377256,"version":"3.55.0"},"reference-count":230,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2020,8,3]],"date-time":"2020-08-03T00:00:00Z","timestamp":1596412800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["Ricerca Corrente 2020"],"award-info":[{"award-number":["Ricerca Corrente 2020"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Which pathogenic mechanisms underlie age-related macular degeneration (AMD)? Are they different for dry and wet variants, or do they stem from common metabolic alterations? Where shall we look for altered metabolism? Is it the inner choroid, or is it rather the choroid\u2013retinal border? Again, since cell-clearing pathways are crucial to degrade altered proteins, which metabolic system is likely to be the most implicated, and in which cell type? Here we describe the unique clearing activity of the retinal pigment epithelium (RPE) and the relevant role of its autophagy machinery in removing altered debris, thus centering the RPE in the pathogenesis of AMD. The cell-clearing systems within the RPE may act as a kernel to regulate the redox homeostasis and the traffic of multiple proteins and organelles toward either the choroid border or the outer segments of photoreceptors. This is expected to cope with the polarity of various domains within RPE cells, with each one owning a specific metabolic activity. A defective clearance machinery may trigger unconventional solutions to avoid intracellular substrates\u2019 accumulation through unconventional secretions. These components may be deposited between the RPE and Bruch\u2019s membrane, thus generating the drusen, which remains the classic hallmark of AMD. These deposits may rather represent a witness of an abnormal RPE metabolism than a real pathogenic component. The empowerment of cell clearance, antioxidant, anti-inflammatory, and anti-angiogenic activity of the RPE by specific phytochemicals is here discussed.<\/jats:p>","DOI":"10.3390\/ijms21155563","type":"journal-article","created":{"date-parts":[[2020,8,4]],"date-time":"2020-08-04T05:56:46Z","timestamp":1596520606000},"page":"5563","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["A Re-Appraisal of Pathogenic Mechanisms Bridging Wet and Dry Age-Related Macular Degeneration Leads to Reconsider a Role for Phytochemicals"],"prefix":"10.3390","volume":"21","author":[{"given":"Roberto","family":"Pinelli","sequence":"first","affiliation":[{"name":"SERI, Switzerland Eye Research Institute, Riva Paradiso 2, 6900 Lugano, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3566-4889","authenticated-orcid":false,"given":"Francesca","family":"Biagioni","sequence":"additional","affiliation":[{"name":"I.R.C.C.S. Neuromed, Via Atinense, 18, 86077 Pozzilli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0185-2099","authenticated-orcid":false,"given":"Fiona","family":"Limanaqi","sequence":"additional","affiliation":[{"name":"Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Roma 55, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miorica","family":"Bertelli","sequence":"additional","affiliation":[{"name":"SERI, Switzerland Eye Research Institute, Riva Paradiso 2, 6900 Lugano, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Scaffidi","sequence":"additional","affiliation":[{"name":"SERI, Switzerland Eye Research Institute, Riva Paradiso 2, 6900 Lugano, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maico","family":"Polzella","sequence":"additional","affiliation":[{"name":"Aliveda Laboratories, Viale Karol Wojtyla 19, 56042 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla Letizia","family":"Busceti","sequence":"additional","affiliation":[{"name":"I.R.C.C.S. Neuromed, Via Atinense, 18, 86077 Pozzilli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3883-5084","authenticated-orcid":false,"given":"Francesco","family":"Fornai","sequence":"additional","affiliation":[{"name":"I.R.C.C.S. Neuromed, Via Atinense, 18, 86077 Pozzilli, Italy"},{"name":"Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Roma 55, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1076\/opep.11.2.67.28158","article-title":"2002 Global update of available data on visual impairment: A compilation of population-based prevalence studies","volume":"11","author":"Pascolini","year":"2004","journal-title":"Ophthalmic Epidemiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1001\/archopht.122.4.477","article-title":"Causes and prevalence of visual impairment among adults in the United States","volume":"122","author":"Congdon","year":"2004","journal-title":"Arch. 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