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Mater."],"published-print":{"date-parts":[[2026,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The lack of physiologically relevant and controllable experimental systems has limited mechanistic understanding of age-related macular degeneration (AMD) and the development of effective therapeutic strategies. Here, we present a tunable\n                    <jats:italic>in vitro<\/jats:italic>\n                    retinal pigment epithelium (RPE) stress model that integrates engineered light delivery with lipid modulation to reproduce early AMD-like cellular pathology under standard culture conditions. Human RPE cells (ARPE-19 and iPSC-derived RPE) were exposed to precisely controlled, low-intensity light-induced oxidative stress in the presence of docosahexaenoic acid (DHA), a highly unsaturated retinal lipid, or palmitic acid (PA) as a saturated lipid control. Cellular responses were assessed using functional and structural readouts including lysosomal and mitochondrial activity, membrane integrity, epithelial morphology, tight junction organization, and lipid peroxidation. A programmable LED-based exposure system enabled fine control over light intensity, duration, and cycling, allowing delivery of sub-lethal, chronic oxidative stress. Combined light and DHA exposure selectively induced lipid peroxidation, disruption of ZO-1\u2013defined tight junctions, and progressive loss of RPE viability, while PA-treated cells and non-retinal HuH7 hepatocytes showed minimal sensitivity. ARPE-19 cells responded rapidly, whereas iPSC-derived RPE cells exhibited delayed but comparable pathological changes, reflecting differences in cellular maturity and stress resilience. Pharmacological inhibition of ferroptosis using ferrostatin-1 significantly reduced lipid peroxidation and rescued epithelial integrity and cell viability, identifying ferroptosis as a key mechanism underlying RPE vulnerability in this system. By enabling programmable and reproducible delivery of oxidative lipid stress, this modular light-based platform provides a biofabrication-compatible framework for modeling early AMD, with potential for integration into more complex retinal constructs, co-culture systems, and high-throughput therapeutic screening pipelines.\n                  <\/jats:p>","DOI":"10.1088\/1748-605x\/ae6498","type":"journal-article","created":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T22:53:55Z","timestamp":1777071235000},"page":"035007","update-policy":"https:\/\/doi.org\/10.1088\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["A tunable, biofabricated light-delivery platform for\n                    <i>in vitro<\/i>\n                    modeling of age-related macular degeneration using iPSC-derived RPE Cells"],"prefix":"10.1088","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-3210-829X","authenticated-orcid":true,"given":"Anwar A","family":"Palakkan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gowthami","family":"Shankar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T P","family":"Vignesh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"266","published-online":{"date-parts":[[2026,5,8]]},"reference":[{"key":"bmmae6498bib1","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1001\/jama.2023.26074","type":"journal-article","article-title":"Age-related macular degeneration: a review","volume":"331","author":"Fleckenstein","year":"2024","journal-title":"JAMA"},{"key":"bmmae6498bib2","doi-asserted-by":"publisher","first-page":"5089","DOI":"10.3390\/molecules27165089","type":"journal-article","article-title":"Recent advances in age-related macular degeneration therapies","volume":"27","author":"Fabre","year":"2022","journal-title":"Molecules"},{"key":"bmmae6498bib3","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.727870","type":"journal-article","article-title":"Functions and diseases of the retinal pigment epithelium","volume":"12","author":"Yang","year":"2021","journal-title":"Front. 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All rights, including for text and data mining, AI training, and similar technologies, are reserved.","name":"copyright_information","label":"Copyright Information"},{"value":"2026-01-29","name":"date_received","label":"Date Received","group":{"name":"publication_dates","label":"Publication dates"}},{"value":"2026-04-24","name":"date_accepted","label":"Date Accepted","group":{"name":"publication_dates","label":"Publication dates"}},{"value":"2026-05-08","name":"date_epub","label":"Online publication date","group":{"name":"publication_dates","label":"Publication dates"}}]}}