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We examined the retina of <jats:italic>kcnj13<\/jats:italic> mutant zebrafish (<jats:italic>obelix<\/jats:italic><jats:sup><jats:italic>td15<\/jats:italic><\/jats:sup>, c.502T\u2009&gt;\u2009C p.[Phe168Leu]) to provide new insights into the pathophysiology underlying these conditions. Detailed phenotyping of <jats:italic>obelix<\/jats:italic><jats:sup><jats:italic>td15<\/jats:italic><\/jats:sup> fish revealed a late onset retinal degeneration at 12 months. Electron microscopy of the <jats:italic>obelix<\/jats:italic><jats:sup><jats:italic>td15<\/jats:italic><\/jats:sup> retinal pigment epithelium (RPE) uncovered reduced phagosome clearance and increased mitochondrial number and size prior any signs of retinal degeneration. Melanosome distribution was also affected in dark-adapted 12-month <jats:italic>obelix<\/jats:italic><jats:sup><jats:italic>td15<\/jats:italic><\/jats:sup> fish. At 6 and 12 months, ATP levels were found to be reduced along with increased expression of glial fibrillary acidic protein and heat shock protein 60. Quantitative RT-PCR of <jats:italic>polg2<\/jats:italic>, <jats:italic>fis1<\/jats:italic>, <jats:italic>opa1<\/jats:italic>, <jats:italic>sod1\/2<\/jats:italic> and <jats:italic>bcl2a<\/jats:italic> from isolated retina showed expression changes consistent with altered mitochondrial activity and retinal stress. We propose that the retinal disease in this model is primarily a failure of phagosome physiology with a secondary mitochondrial dysfunction. Our findings suggest that alterations in the RPE and photoreceptor cellular organelles may contribute to <jats:italic>KCNJ13<\/jats:italic>-related retinal degeneration and provide a therapeutic target.<\/jats:p>","DOI":"10.1038\/s41598-019-40507-8","type":"journal-article","created":{"date-parts":[[2019,3,7]],"date-time":"2019-03-07T11:04:07Z","timestamp":1551956647000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Phagosomal and mitochondrial alterations in RPE may contribute to KCNJ13 retinopathy"],"prefix":"10.1038","volume":"9","author":[{"given":"Maria","family":"Toms","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Burgoyne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dhani","family":"Tracey-White","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rose","family":"Richardson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam M.","family":"Dubis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew R.","family":"Webster","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clare","family":"Futter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1688-5360","authenticated-orcid":false,"given":"Mariya","family":"Moosajee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,3,7]]},"reference":[{"key":"40507_CR1","doi-asserted-by":"publisher","first-page":"995","DOI":"10.1016\/S0896-6273(00)80480-8","volume":"20","author":"G Krapivinsky","year":"1998","unstructured":"Krapivinsky, G. et al. 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