{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T07:20:16Z","timestamp":1792653616847,"version":"4.5.0"},"reference-count":57,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,11,3]],"date-time":"2021-11-03T00:00:00Z","timestamp":1635897600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Age-related Macular degeneration (AMD) is a degenerative disease of the macula affecting the elderly population. Treatment options are limited, partly due to the lack of understanding of AMD pathology and the lack of suitable research models that replicate the complexity of the human macula and the intricate interplay of the genetic, aging and lifestyle risk factors contributing to AMD. One of the main genetic risks associated with AMD is located on the Complement Factor H (CFH) gene, leading to an amino acid substitution in the Factor H (FH) protein (Y402H). However, the mechanism of how this FH variant promotes the onset of AMD remains unclear. Previously, we have shown that FH deprivation in RPE cells, via CFH silencing, leads to increased inflammation, metabolic impairment and vulnerability toward oxidative stress. In this study, we established a novel co-culture model comprising CFH silenced RPE cells and porcine retinal explants derived from the visual streak of porcine eyes, which closely resemble the human macula. We show that retinae exposed to FH-deprived RPE cells show signs of retinal degeneration, with rod cells being the first cells to undergo degeneration. Moreover, via Raman analyses, we observed changes involving the mitochondria and lipid composition of the co-cultured retinae upon FH loss. Interestingly, the detrimental effects of FH loss in RPE cells on the neuroretina were independent of glial cell activation and external complement sources. Moreover, we show that the co-culture model is also suitable for human retinal explants, and we observed a similar trend when RPE cells deprived of FH were co-cultured with human retinal explants from a single donor eye. Our findings highlight the importance of RPE-derived FH for retinal homeostasis and provide a valuable model for AMD research.<\/jats:p>","DOI":"10.3390\/biom11111621","type":"journal-article","created":{"date-parts":[[2021,11,3]],"date-time":"2021-11-03T17:59:38Z","timestamp":1635962378000},"page":"1621","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Complement Factor H Loss in RPE Cells Causes Retinal Degeneration in a Human RPE-Porcine Retinal Explant Co-Culture Model"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6357-1500","authenticated-orcid":false,"given":"Angela","family":"Armento","sequence":"first","affiliation":[{"name":"Institute for Ophthalmic Research, Department for Ophthalmology, Eberhard Karls University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aparna","family":"Murali","sequence":"additional","affiliation":[{"name":"Institute for Ophthalmic Research, Department for Ophthalmology, Eberhard Karls University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"},{"name":"Faculty of Medicine, University of Queensland, Herston, QLD 4006, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1545-5430","authenticated-orcid":false,"given":"Julia","family":"Marzi","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Engineering, Department for Medical Technologies and Regenerative Medicine, Eberhard Karls University T\u00fcbingen, 72076 T\u00fcbingen, Germany"},{"name":"NMI Natural and Medical Sciences Institute at the University of T\u00fcbingen, 72770 Reutlingen, Germany"},{"name":"Cluster of Excellence iFIT (EXC 2180) \u201cImage-Guided and Functionally Instructed Tumor Therapies\u201d, Eberhard Karls University T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana C","family":"Almansa-Garcia","sequence":"additional","affiliation":[{"name":"Institute for Ophthalmic Research, Department for Ophthalmology, Eberhard Karls University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9045-182X","authenticated-orcid":false,"given":"Blanca","family":"Arango-Gonzalez","sequence":"additional","affiliation":[{"name":"Institute for Ophthalmic Research, Department for Ophthalmology, Eberhard Karls University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen","family":"Kilger","sequence":"additional","affiliation":[{"name":"Institute for Ophthalmic Research, Department for Ophthalmology, Eberhard Karls University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8394-8355","authenticated-orcid":false,"given":"Simon J","family":"Clark","sequence":"additional","affiliation":[{"name":"Institute for Ophthalmic Research, Department for Ophthalmology, Eberhard Karls University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"},{"name":"Lydia Becker Institute of Immunology and Inflammation, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"Schenke-Layland","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Engineering, Department for Medical Technologies and Regenerative Medicine, Eberhard Karls University T\u00fcbingen, 72076 T\u00fcbingen, Germany"},{"name":"NMI Natural and Medical Sciences Institute at the University of T\u00fcbingen, 72770 Reutlingen, Germany"},{"name":"Cluster of Excellence iFIT (EXC 2180) \u201cImage-Guided and Functionally Instructed Tumor Therapies\u201d, Eberhard Karls University T\u00fcbingen, 72076 T\u00fcbingen, Germany"},{"name":"Department of Medicine\/Cardiology, Cardiovascular Research Laboratories, David Geffen School of Medicine at University of California, Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charmaine A","family":"Ramlogan-Steel","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Queensland, Herston, QLD 4006, Australia"},{"name":"School of Health, Medical and Applied Sciences, Central Queensland University, Brisbane, QLD 4000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason C","family":"Steel","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Queensland, Herston, QLD 4006, Australia"},{"name":"School of Health, Medical and Applied Sciences, Central Queensland University, Brisbane, QLD 4000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2209-2113","authenticated-orcid":false,"given":"Marius","family":"Ueffing","sequence":"additional","affiliation":[{"name":"Institute for Ophthalmic Research, Department for Ophthalmology, Eberhard Karls University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1002\/path.4266","article-title":"Mechanisms of age-related macular degeneration and therapeutic opportunities","volume":"232","author":"Campagne","year":"2014","journal-title":"J. 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