ArticleDrug metabolism and disposition: the biological fate of chemicals2018
Retinal Cholesterol Content Is Reduced in Simvastatin-Treated Mice Due to Inhibited Local Biosynthesis Albeit Increased Uptake of Serum Cholesterol.
Article in Drug metabolism and disposition: the biological fate of chemicals, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 41 citations in OpenAlex.
- Retinal phenotype of APOB100 transgenic mice on a Western diet with human-like hyperlipidemia and cholesterol crystals in the retina and choroid.Lab animal · 2026Article
- Association Between Macular Ganglion Cell-Inner Plexiform Layer and Non-Proliferative Retinopathy Without Macular Edema in Type 2 Diabetes via Diabetes Duration and HbABiomedicines · 2025Article
- Bottlenecks in the Investigation of Retinal Sterol Homeostasis.Biomolecules · 2024Review
- Review
- APOB100 transgenic mice exemplify how the systemic circulation content may affect the retina without altering retinal cholesterol input.Cellular and molecular life sciences : CMLS · 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
- Quantitative characterizations of the cholesterol-related pathways in the retina and brain of hamsters.Journal of lipid research · 2023Article
- Repurposing medications for treatment of age-related macular degeneration: Insights from novel approaches to data mining.Experimental biology and medicine (Maywood, N.J.) · 2023Review
- Statin drugs enhance responses to immune checkpoint blockade in head and neck cancer models.Journal for immunotherapy of cancer · 2023Article
- Review
- Dyslipidemia in age-related macular degeneration.Eye (London, England) · 2022Review
- Low-Dose Anti-HIV Drug Efavirenz Mitigates Retinal Vascular Lesions in a Mouse Model of Alzheimer's Disease.Frontiers in pharmacology · 2022Article
- Characterizations of Hamster Retina as a Model for Studies of Retinal Cholesterol Homeostasis.Biology · 2021Article
- Renal function and lipid metabolism are major predictors of circumpapillary retinal nerve fiber layer thickness-the LIFE-Adult Study.BMC medicine · 2021Article
- Preliminary Investigation on Simvastatin-Loaded Polymeric Micelles in View of the Treatment of the Back of the Eye.Pharmaceutics · 2021Article
- Studies of ApoDCellular and molecular life sciences : CMLS · 2021Article
- Statins for the prevention of proliferative vitreoretinopathy: cellular responses in cultured cells and clinical statin concentrations in the vitreous.Scientific reports · 2021Article
- The Interplay between Retinal Pathways of Cholesterol Output and Its Effects on Mouse Retina.Biomolecules · 2019Article
- RORγ is a targetable master regulator of cholesterol biosynthesis in a cancer subtype.Nature communications · 2019Article
- Simvastatin protects photoreceptors from oxidative stress induced by all-trans-retinal, through the up-regulation of interphotoreceptor retinoid binding protein.British journal of pharmacology · 2019Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Statins, a class of cholesterol-lowering drugs, are currently being investigated for treatment of age-related macular degeneration, a retinal disease. Herein, retinal and serum concentrations of four statins (atorvastatin, simvastatin, pravastatin, and rosuvastatin) were evaluated after mice were given a single drug dose of 60 mg/kg body weight. All statins, except rosuvastatin, were detected in the retina: atorvastatin and pravastatin at 1.6 pmol and simvastatin at 4.1 pmol. Serum statin concentrations (pmol/ml) were 223 (simvastatin), 1401 (atorvastatin), 2792 (pravastatin), and 9050 (rosuvastatin). Simvastatin was then administered to mice daily for 6 weeks at 60 mg/kg body weight. Simvastatin treatment reduced serum cholesterol levels by 18% and retinal content of cholesterol and lathosterol (but not desmosterol) by 24% and 21%, respectively. The relative contributions of retinal cholesterol biosynthesis and retinal uptake of serum cholesterol to total retinal cholesterol input were changed as well. These contributions were 79% and 21%, respectively, in vehicle-treated mice and 69% and 31%, respectively, in simvastatin-treated mice. Thus, simvastatin treatment lowered retinal cholesterol because a compensatory upregulation of retinal uptake of serum cholesterol was not sufficient to overcome the effect of inhibited retinal biosynthesis. Simultaneously, simvastatin-treated mice had a 2.9-fold increase in retinal expression of
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