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Dysregulation of retinal lipid homeostasis due to normal aging or age\u2010related disease triggers lipid accumulation within the RPE, on Bruch's membrane (BrM), and in the subretinal space. In its role as a hub for lipid trafficking into and out of the neural retina, the RPE packages a significant amount of lipid into lipid droplets for storage and into apolipoprotein B (APOB)\u2010containing lipoproteins (Blps) for export. Microsomal triglyceride transfer protein (MTP), encoded by the\n                    <jats:italic>MTTP<\/jats:italic>\n                    gene, is essential for Blp assembly. Herein we test the hypothesis that MTP expression in the RPE is essential to maintain lipid balance and retinal function using the newly generated\n                    <jats:italic>RPE\u0394Mttp<\/jats:italic>\n                    mouse model. Using non\u2010invasive ocular imaging, electroretinography, and histochemical and biochemical analyses we show that genetic depletion of\n                    <jats:italic>Mttp<\/jats:italic>\n                    from the RPE results in intracellular lipid accumulation, increased photoreceptor\u2010associated cholesterol deposits, and photoreceptor cell death, and loss of rod but not cone function. RPE\u2010specific reduction in Mttp had no significant effect on plasma lipids and lipoproteins. While APOB was decreased in the RPE, most ocular retinoids remained unchanged, with the exception of the storage form of retinoid, retinyl ester. Thus suggesting that RPE MTP is critical for Blp synthesis and assembly but is not directly involved in plasma lipoprotein metabolism. These studies demonstrate that RPE\u2010specific MTP expression is necessary to establish and maintain retinal lipid homeostasis and visual function.\n                  <\/jats:p>","DOI":"10.1096\/fj.202302491r","type":"journal-article","created":{"date-parts":[[2024,3,6]],"date-time":"2024-03-06T06:29:37Z","timestamp":1709706577000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Microsomal triglyceride transfer protein is necessary to maintain lipid homeostasis and retinal function"],"prefix":"10.1096","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6314-8980","authenticated-orcid":false,"given":"Catharina R.","family":"Grubaugh","sequence":"first","affiliation":[{"name":"Department of Basic and Translational Sciences University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-5720-3923","authenticated-orcid":false,"given":"Anuradha","family":"Dhingra","sequence":"additional","affiliation":[{"name":"Department of Basic and Translational Sciences University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3499-7614","authenticated-orcid":false,"given":"Binu","family":"Prakash","sequence":"additional","affiliation":[{"name":"Department of Foundations of Medicine New York University Grossman Long Island School of Medicine  Mineola New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6892-7492","authenticated-orcid":false,"given":"Diego","family":"Montenegro","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Columbia University  New York New York USA"},{"name":"Department of Pathology and Cell Biology Columbia University  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7448-5950","authenticated-orcid":false,"given":"Janet R.","family":"Sparrow","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Columbia University  New York New York USA"},{"name":"Department of Pathology and Cell Biology Columbia University  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9397-0342","authenticated-orcid":false,"given":"Lauren L.","family":"Daniele","sequence":"additional","affiliation":[{"name":"Department of Basic and Translational Sciences University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9769-1538","authenticated-orcid":false,"given":"Christine A.","family":"Curcio","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, Heersink School of Medicine University of Alabama at Birmingham  Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2827-1892","authenticated-orcid":false,"given":"Brent A.","family":"Bell","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9663-300X","authenticated-orcid":false,"given":"M. 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