ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2024
Microsomal triglyceride transfer protein is necessary to maintain lipid homeostasis and retinal function.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 13 citations in OpenAlex.
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- Polyunsaturated fatty acid metabolism in the retinal pigment epithelium and its association with outer retinal disease.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Review
- The Science of Rod-Mediated Dark Adaptation, an Outcome Measure for Age-Related Macular Degeneration: The 2025 Proctor Medal Lecture.Investigative ophthalmology & visual science · 2026Article
- Tracking Systemic and Ocular Vitamin A.Cells · 2026Article
- Single-cell transcriptome and surfaceome profiling of the adult human retinal pigment epithelium.Stem cell reports · 2025Article
- Cholesteryl Ester Transfer Protein Deficiency and Hyperalphalipoproteinemia.Journal of atherosclerosis and thrombosis · 2025Review
- Glycolipids implicated as mediators of clinically visible retinal pigment epithelial migration in age-related macular degeneration.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- DNMT1/MTTP axis promotes gastritis progression duringEpigenomics · 2025Article
- The intestine-specific homeobox (ISX) modulates β-carotene-dependent regulation of microsomal triglyceride transfer protein (MTP) in a tissue-specific manner.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2025Article
- Abetalipoproteinemia with angioid streaks, choroidal neovascularization, atrophy, and extracellular deposits revealed by multimodal retinal imaging.Ophthalmic genetics · 2024Article
- Article
- Drusen in AMD from the Perspective of Cholesterol Metabolism and Hypoxic Response.Journal of clinical medicine · 2024Review
- Age-Related Macular Degeneration, a Mathematically Tractable Disease.Investigative ophthalmology & visual science · 2024Review
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.