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Here, these effects on photoreceptor outer segment (POS) trafficking in the retinal pigment epithelium (RPE), a major pathway of disease underlying irreversible sight\u2010loss, are studied.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>POS trafficking is studied in ARPE\u201019 cells using an algorithm\u2010based quantification of confocal\u2010immunofluorescence data supported by ultrastructural studies. It is shown that although POS are tightly regulated and trafficked via Rab5, Rab7 vesicles, LAMP1\/2 lysosomes and LC3b\u2010autophagosomes, there is also a considerable degree of variation and flexibility in this process. Treatment with H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> and bafilomycin A<jats:sup>1<\/jats:sup> reveals that oxidative stress and dysregulated autophagy target intracellular compartments and trafficking in strikingly different ways. These effects appear limited to POS\u2010containing vesicles, suggesting a cargo\u2010specific effect.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The findings offer insights into how RPE cells cope with stress, and how mechanisms influencing POS transport\/degradation can have different outcomes in the senescent retina. These shed new light on cellular processes underlying retinopathies such as age\u2010related macular degeneration. The discoveries reveal how diet and nutrition can cause fundamental alterations at a cellular level, thus contributing to a better understanding of the diet\u2010disease axis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mnfr.201800951","type":"journal-article","created":{"date-parts":[[2019,3,5]],"date-time":"2019-03-05T22:14:08Z","timestamp":1551824048000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Oxidative Stress and Dysfunctional Intracellular Traffic Linked to an Unhealthy Diet Results in Impaired Cargo Transport in the Retinal Pigment Epithelium (RPE)"],"prefix":"10.1002","volume":"63","author":[{"given":"Eloise","family":"Keeling","sequence":"first","affiliation":[{"name":"Clinical and Experimental Sciences Faculty of Medicine University of Southampton  MP806, Tremona Road SO16 6YD UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David S.","family":"Chatelet","sequence":"additional","affiliation":[{"name":"Biomedical Imaging Unit University of Southampton  MP12, Tremona Road SO16 6YD UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Johnston","sequence":"additional","affiliation":[{"name":"Biomedical Imaging Unit University of Southampton  MP12, Tremona Road SO16 6YD UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anton","family":"Page","sequence":"additional","affiliation":[{"name":"Biomedical Imaging Unit University of Southampton  MP12, Tremona Road SO16 6YD UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Tumbarello","sequence":"additional","affiliation":[{"name":"Biological Sciences Faculty of Natural &amp; Environmental Sciences University of Southampton  Life Sciences Building 85 SO17 1BJ UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew J.","family":"Lotery","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Sciences Faculty of Medicine University of Southampton  MP806, Tremona Road SO16 6YD UK"},{"name":"Eye Unit University Hospital Southampton NHS Foundation Trust  Southampton SO16 6YD UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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