{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Grubaugh CR"],"funding":["NEI NIH HHS","National Eye Institute","National Heart, Lung, and Blood Institute","NHLBI NIH HHS","BrightFocus Foundation"],"pagination":["e23522"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10949407"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["38(5)"],"pubmed_abstract":["Lipid processing by the retinal pigment epithelium (RPE) is necessary to maintain retinal health and function. Dysregulation of retinal lipid homeostasis due to normal aging or age-related 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)-containing lipoproteins (Blps) for export. Microsomal triglyceride transfer protein (MTP), encoded by the MTTP 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 RPEΔMttp mouse model. Using non-invasive ocular imaging, electroretinography, and histochemical and biochemical analyses we show that genetic depletion of Mttp from the RPE results in intracellular lipid accumulation, increased photoreceptor-associated cholesterol deposits, and photoreceptor cell death, and loss of rod but not cone function. RPE-specific 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-specific MTP expression is necessary to establish and maintain retinal lipid homeostasis and visual function."],"journal":["FASEB journal : official publication of the Federation of American Societies for Experimental Biology"],"pubmed_title":["Microsomal triglyceride transfer protein is necessary to maintain lipid homeostasis and retinal function."],"pmcid":["PMC10949407"],"funding_grant_id":["P30 EY001583","R21 EY032743","M2023002F","R01 EY026525","R01 HL166214","P01 HL160470","EY0323743","HL160470"],"pubmed_authors":["Montenegro D","Daniele LL","Prakash B","Bell BA","Dhingra A","Hussain MM","Curcio CA","Boesze-Battaglia K","Grubaugh CR","Sparrow JR"],"additional_accession":[]},"is_claimable":false,"name":"Microsomal triglyceride transfer protein is necessary to maintain lipid homeostasis and retinal function.","description":"Lipid processing by the retinal pigment epithelium (RPE) is necessary to maintain retinal health and function. Dysregulation of retinal lipid homeostasis due to normal aging or age-related 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)-containing lipoproteins (Blps) for export. Microsomal triglyceride transfer protein (MTP), encoded by the MTTP 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 RPEΔMttp mouse model. Using non-invasive ocular imaging, electroretinography, and histochemical and biochemical analyses we show that genetic depletion of Mttp from the RPE results in intracellular lipid accumulation, increased photoreceptor-associated cholesterol deposits, and photoreceptor cell death, and loss of rod but not cone function. RPE-specific 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-specific MTP expression is necessary to establish and maintain retinal lipid homeostasis and visual function.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Mar","modification":"2025-04-04T01:29:09.552Z","creation":"2025-04-04T01:29:09.552Z"},"accession":"S-EPMC10949407","cross_references":{"pubmed":["38445789"],"doi":["10.1096/fj.202302491R","10.1096/fj.202302491r"]}}