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Wildtype mice are given a high fat diet (HFD) to determine how unhealthy foods can bring about retinal degeneration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>Following weaning, female C57BL\/6 mice are maintained on standard chow (7%\u00a0kcal fat, <jats:italic>n<\/jats:italic> = 29) or a HFD (45%\u00a0kcal fat, <jats:italic>n<\/jats:italic> = 27) for 12 months. Animals were sacrificed following electroretinography (ERG) and their eyes analyzed by histology, confocal immunofluorescence, and transmission electron microscopy. HFD mice become obese, but showed normal retinal function compared to chow\u2010fed controls. However, diminished \u03b23tubulin labeling of retinal cross\u2010sections indicated fewer\/damaged neuronal processes in the inner plexiform layer. AMD\u2010linked proteins clusterin and TIMP3 accumulated in the retinal pigment epithelium (RPE) and Bruch's membrane (BrM). Neutral lipids also deposited in the outer retinae of HFD mice. Ultrastructural analysis revealed disorganized photoreceptor outer segments, collapsed\/misaligned RPE microvilli, vacuoles, convoluted basolateral RPE infolds and BrM changes. Basal laminar\u2010like deposits were also present alongside abnormal choroidal endothelial cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We show that prolonged exposure to an unhealthy \u201cWestern\u2010style\u201d diet alone can recapitulate early\u2010intermediate AMD\u2010like features in wildtype mice, highlighting the importance of diet and nutrition in the etiology of sight\u2010loss.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mnfr.202100823","type":"journal-article","created":{"date-parts":[[2022,3,20]],"date-time":"2022-03-20T03:14:00Z","timestamp":1647746040000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["A High Fat \u201cWestern\u2010style\u201d Diet Induces AMD\u2010Like Features in Wildtype Mice"],"prefix":"10.1002","volume":"66","author":[{"given":"Eloise","family":"Keeling","sequence":"first","affiliation":[{"name":"Clinical and Experimental Sciences Faculty of Medicine University of Southampton  MP806, Tremona Road Southampton SO16 6YD UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Savannah A.","family":"Lynn","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Sciences Faculty of Medicine University of Southampton  MP806, Tremona Road Southampton SO16 6YD UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yen Min","family":"Koh","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Sciences Faculty of Medicine University of Southampton  MP806, Tremona Road Southampton SO16 6YD UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny A.","family":"Scott","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Sciences Faculty of Medicine University of Southampton  MP806, Tremona Road Southampton SO16 6YD UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron","family":"Kendall","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Sciences Faculty of Medicine University of Southampton  MP806, Tremona Road Southampton SO16 6YD UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maureen","family":"Gatherer","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Sciences Faculty of Medicine University of Southampton  MP806, Tremona Road Southampton 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 Southampton SO16 6YD UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felino R.","family":"Cagampang","sequence":"additional","affiliation":[{"name":"Human Development and Health Faculty of Medicine University of Southampton  Southampton General Hospital, Tremona Road Southampton SO16 6YD 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 Southampton SO16 6YD UK"},{"name":"Eye Unit University Hospital Southampton NHS Foundation Trust  Southampton SO16 6YD UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1027-6938","authenticated-orcid":false,"given":"J. 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