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It involves the degeneration of the retinal pigment epithelium (RPE) and the accumulation of deposits between the RPE and the Bruch's membrane (BrM), ultimately leading to photoreceptor death. The multifactorial and chronic nature of AMD makes it challenging to model in\u00a0vitro. We developed a biomaterial based on decellularized BrM (dECM\u2010BrM) from aged donors to evaluate its ability to induce an AMD\u2010like phenotype in RPE monolayers. BrM from 5 young and 5 aged human donors was decellularized and the protein profile analyzed by LC\u2013MS\/MS. dECM\u2010BrM was then used as a coating substrate for RPE culture. A total of 281 proteins were identified and proteomic analysis screened 49 differentially expressed proteins in aged dECM\u2010BrM. Gene Ontology analysis showed that they were associated with extracellular region, antioxidant activity, lipid metabolism and transport. Moreover, the KEGG pathway related to complement and coagulation cascade was significantly enriched. RPE culture on aged dECM\u2010BrM allowed RPE polarization and after 60\u2009days, transepithelial electrical resistance significantly decreased compared to RPE grown on young dECM\u2010BrM, accompanied by increased IL\u201033 secretion and marked expression of drusen components such as vitronectin and apolipoprotein E, lipid deposition and complement factors C3 and C9. We showed a successful approach to obtain a BrM mimic based on decellularized BrM that ensured cellular removal while preserving ECM structure and identified differentially expressed proteins in aged dECM\u2010BrM that may provide specific biochemical cues fundamental to model AMD in\u00a0vitro.<\/jats:p>","DOI":"10.1111\/acel.70501","type":"journal-article","created":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T16:45:17Z","timestamp":1777049117000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Decellularized Aged Bruch's Membrane Confers Unique Biochemical Cues to Retinal Pigment Epithelium for In\u00a0Vitro Modeling of Age\u2010Related Macular Degeneration"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0941-9134","authenticated-orcid":false,"given":"Blanca","family":"Molins","sequence":"first","affiliation":[{"name":"Group of Ocular Inflammation: Clinical and Experimental Studies Institut D'investigacions Biom\u00e8diques Agust\u00ed Pi i Sunyer (IDIBAPS)  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mercedes Soledad","family":"Nabaes Jodar","sequence":"additional","affiliation":[{"name":"Group of Ocular Inflammation: Clinical and Experimental Studies Institut D'investigacions Biom\u00e8diques Agust\u00ed Pi i Sunyer (IDIBAPS)  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliandre","family":"de Oliveira","sequence":"additional","affiliation":[{"name":"Proteomics Laboratory, Biomolecular Analysis Unit. Scientifical and Technological Centers University of Barcelona  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josep Maria","family":"Estanyol","sequence":"additional","affiliation":[{"name":"Proteomics Laboratory, Biomolecular Analysis Unit. Scientifical and Technological Centers University of Barcelona  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"Pe\u00f1a","sequence":"additional","affiliation":[{"name":"Research Institute Sant Pau (IR SANT PAU) CIBERCV  Barcelona Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaione","family":"Bezunartea","sequence":"additional","affiliation":[{"name":"Retinal Pathologies and New Therapies Group, Experimental Ophthalmology Laboratory, Department of Ophthalmology Cl\u00ednica Universidad de Navarra  Pamplona Spain"},{"name":"Navarra Institute for Health Research IdiSNA  Pamplona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Retinal Pathologies and New Therapies Group, Experimental Ophthalmology Laboratory, Department of Ophthalmology Cl\u00ednica Universidad de Navarra  Pamplona 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