ArticleThe Journal of biological chemistry2016
Retinal Hypercholesterolemia Triggers Cholesterol Accumulation and Esterification in Photoreceptor Cells.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 52 citations in OpenAlex.
- The observation of retinal microvascular alterations in familial hypercholesterolemia patients through optical coherence tomography angiography.International ophthalmology · 2025Article
- Myeloid ACAT1/SOAT1: a novel regulator of dyslipidemia and retinal neovascularization.npj metabolic health and disease · 2025Review
- Association between Disorders of Lipid Metabolism and Oculopathy: An Overview.International journal of medical sciences · 2025Review
- Evaluating the Impact of Retinal Vessel Segmentation Metrics on Retest Reliability in a Clinical Setting: A Comparative Analysis Using AutoMorph.Investigative ophthalmology & visual science · 2024Article
- Aberrant lipid accumulation and retinal pigment epithelium dysfunction in PRCD-deficient mice.Experimental eye research · 2024Article
- The normalizing effects of the CYP46A1 activator efavirenz on retinal sterol levels and risk factors for glaucoma in ApojCellular and molecular life sciences : CMLS · 2023Article
- Oxygen-induced pathological angiogenesis promotes intense lipid synthesis and remodeling in the retina.iScience · 2023Article
- Mass spectrometry-based retina proteomics.Mass spectrometry reviews · 2023Review
- Role of acyl-coenzyme A: cholesterol transferase 1 (ACAT1) in retinal neovascularization.Journal of neuroinflammation · 2023Article
- Cholesterol and oxysterols in retinal neuron-glia interactions: relevance for glaucoma.Frontiers in ophthalmology · 2023Review
- 2-Hydroxypropyl-β-cyclodextrin reduces retinal cholesterol in wild-type and Cyp27a1British journal of pharmacology · 2021Article
- Localization of sterols and oxysterols in mouse brain reveals distinct spatial cholesterol metabolism.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- LXRs regulate features of age-related macular degeneration and may be a potential therapeutic target.JCI insight · 2020Article
- The Interplay between Retinal Pathways of Cholesterol Output and Its Effects on Mouse Retina.Biomolecules · 2019Article
- Retinal Vascular Abnormalities and Microglia Activation in Mice with Deficiency in Cytochrome P450 46A1-Mediated Cholesterol Removal.The American journal of pathology · 2019Article
- The Question of a Role for Statins in Age-Related Macular Degeneration.International journal of molecular sciences · 2018Review
- Disrupted cholesterol metabolism promotes age-related photoreceptor neurodegeneration.Journal of lipid research · 2018Article
- Soft Drusen in Age-Related Macular Degeneration: Biology and Targeting Via the Oil Spill Strategies.Investigative ophthalmology & visual science · 2018Review
- Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The process of vision is impossible without the photoreceptor cells, which have a unique structure and specific maintenance of cholesterol. Herein we report on the previously unrecognized cholesterol-related pathway in the retina discovered during follow-up characterizations of Cyp27a1(-/-)Cyp46a1(-/-) mice. These animals have retinal hypercholesterolemia and convert excess retinal cholesterol into cholesterol esters, normally present in the retina in very small amounts. We established that in the Cyp27a1(-/-)Cyp46a1(-/-) retina, cholesterol esters are generated by and accumulate in the photoreceptor outer segments (OS), which is the retinal layer with the lowest cholesterol content. Mouse OS were also found to express the cholesterol-esterifying enzyme acyl-coenzyme A:cholesterol acyltransferase (ACAT1), but not lecithin-cholesterol acyltransferase (LCAT), and to differ from humans in retinal expression of ACAT1. Nevertheless, cholesterol esters were discovered to be abundant in human OS. We suggest a mechanism for cholesterol ester accumulation in the OS and that activity impairment of ACAT1 in humans may underlie the development of subretinal drusenoid deposits, a hallmark of age-related macular degeneration, which is a common blinding disease. We generated Cyp27a1(-/-)Cyp46a1(-/-)Acat1(-/-) mice, characterized their retina by different imaging modalities, and confirmed that unesterified cholesterol does accumulate in their OS and that there is photoreceptor apoptosis and OS degeneration in this line. Our results provide insights into the retinal response to local hypercholesterolemia and the retinal significance of cholesterol esterification, which could be cell-specific and both beneficial and detrimental for retinal structure and function.
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Registered trials
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