ArticleExperimental eye research2016
Differential cytotoxic effects of 7-dehydrocholesterol-derived oxysterols on cultured retina-derived cells: Dependence on sterol structure, cell type, and density.
Article in Experimental eye research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 41 citations in OpenAlex.
- Review
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- Synthesis, Properties, and Biocompatibility of 4-Carboxyphenyboronic Acid-Modified Gelatin-Methacryloyl: A Hydrogel for Retinal Surgeries.ACS omega · 2024Article
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- MicroRNA-152-3p and MicroRNA-196a-5p Are Downregulated When Müller Cells Are Promoted by Components of the Internal Limiting Membrane: Implications for Macular Hole Healing.International journal of molecular sciences · 2023Article
- MicroRNA-based engineering of mesenchymal stem cell extracellular vesicles for treatment of retinal ischemic disorders: Engineered extracellular vesiclesand retinal ischemia.Acta biomaterialia · 2023Article
- Dose-Response Effects of 7-Dehydrocholesterol Reductase Inhibitors on Sterol Profiles and Vesicular Stomatitis Virus Replication.ACS pharmacology & translational science · 2022Article
- Article
- Metoprolol Inhibits Developmental Brain Sterol Biosynthesis in Mice.Biomolecules · 2022Article
- Individual and simultaneous treatment with antipsychotic aripiprazole and antidepressant trazodone inhibit sterol biosynthesis in the adult brain.Journal of lipid research · 2022Article
- Sterol regulation of developmental and oncogenic Hedgehog signaling.Biochemical pharmacology · 2022Review
- Medication effects on developmental sterol biosynthesis.Molecular psychiatry · 2022Review
- Morphological, biochemical, and transcriptomic characterization of iPSC-derived human RPE cells from normal and Smith-Lemli-Opitz syndrome patients.Molecular vision · 2022Article
- Transcriptomic Changes Associated with Loss of Cell Viability Induced by Oxysterol Treatment of a Retinal Photoreceptor-Derived Cell Line: An In Vitro Model of Smith-Lemli-Opitz Syndrome.International journal of molecular sciences · 2021Article
- Prescription Medications Alter Neuronal and Glial Cholesterol Synthesis.ACS chemical neuroscience · 2021Article
- Reactive Sterol Electrophiles: Mechanisms of Formation and Reactions with Proteins and Amino Acid Nucleophiles.Chemistry (Basel, Switzerland) · 2020Article
- VEGF Upregulates EGFR Expression to Stimulate Chemotactic Behaviors in the rMC-1 Model of Müller Glia.Brain sciences · 2020Article
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Tissue accumulation of 7-dehydrocholesterol (7DHC) is a hallmark of Smith-Lemli-Opitz Syndrome (SLOS), a human inborn error of the cholesterol (CHOL) synthesis pathway. Retinal 7DHC-derived oxysterol formation occurs in the AY9944-induced rat model of SLOS, which exhibits a retinal degeneration characterized by selective loss of photoreceptors and associated functional deficits, Müller cell hypertrophy, and engorgement of the retinal pigment epithelium (RPE) with phagocytic inclusions. We evaluated the relative effects of four 7DHC-derived oxysterols on three retina-derived cell types in culture, with respect to changes in cellular morphology and viability. 661W (photoreceptor-derived) cells, rMC-1 (Müller glia-derived) cells, and normal diploid monkey RPE (mRPE) cells were incubated for 24 h with dose ranges of either 7-ketocholesterol (7kCHOL), 5,9-endoperoxy-cholest-7-en-3β,6α-diol (EPCD), 3β,5α-dihydroxycholest-7-en-6-one (DHCEO), or 4β-hydroxy-7-dehydrocholesterol (4HDHC); CHOL served as a negative control (same dose range), along with appropriate vehicle controls, while staurosporine (Stsp) was used as a positive cytotoxic control. For 661W cells, the rank order of oxysterol potency was: EPCD > 7kCHOL >> DHCEO > 4HDHC ≈ CHOL. EC50 values were higher for confluent vs. subconfluent cultures. 661W cells exhibited much higher sensitivity to EPCD and 7kCHOL than either rMC-1 or mRPE cells, with the latter being the most robust when challenged, either at confluence or in sub-confluent cultures. When tested on rMC-1 and mRPE cells, EPCD was again an order of magnitude more potent than 7kCHOL in compromising cellular viability. Hence, 7DHC-derived oxysterols elicit differential cytotoxicity that is dose-, cell type-, and cell density-dependent. These results are consistent with the observed progressive, photoreceptor-specific retinal degeneration in the rat SLOS model, and support the hypothesis that 7DHC-derived oxysterols are causally linked to that retinal degeneration as well as to SLOS.
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Registered trials
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