title: Pathways of cholesterol homeostasis in mouse retina responsive to dietary and pharmacologic treatments.
abstract: Effects of serum cholesterol on cholesterol content in the retina are currently unknown. It is also unclear how cholesterol levels are controlled in the retina. High-cholesterol diet and oral administrations of simvastatin were used to modulate serum cholesterol in mice. These treatments only modestly affected cholesterol content in the retina and had no significant effect on retinal expression of the major cholesterol- and vision-related genes; the sterol-regulatory element binding protein pathway of transcriptional regulation does not seem to be operative in the retina under the experimental conditions used. Evidence is obtained that posttranslational mechanisms play a role in the control of retinal cholesterol. Retinal genes were only upregulated by oral administrations of TO901317 activating liver X receptors. Three of the upregulated genes could be of particular importance (apoD, Idol, and Rpe65) and have not yet been considered in the context of cholesterol homeostasis in the retina. Collectively, the data obtained identify specific features of retinal cholesterol maintenance and suggest additional therapies for age-related macular degeneration, a blinding disease characterized by cholesterol and lipid accumulations in chorioretinal tissues.
authors.affiliation: Department of Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, OH 44106.
authors.forename: Wenchao
authors.initials: W
authors.lastname: Zheng
authors.affiliation: Department of Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, OH 44106.
authors.forename: Natalia
authors.initials: N
authors.lastname: Mast
authors.affiliation: Department of Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, OH 44106.
authors.forename: Aicha
authors.initials: A
authors.lastname: Saadane
authors.affiliation: Department of Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, OH 44106.
authors.forename: Irina A
authors.initials: IA
authors.lastname: Pikuleva
mesh_terms: D000818:Animals; D053399:Apolipoproteins D / Q000235:genetics; D002784:Cholesterol / Q000378:metabolism*; D004032:Diet / Q000009:adverse effects*; D005260:Female; D006706:Homeostasis / Q000187:drug effects*; D006845:Hydrocarbons, Fluorinated / Q000494:pharmacology*; D000071518:Liver X Receptors; D051379:Mice; D057093:Orphan Nuclear Receptors / Q000819:agonists; D012160:Retina / Q000187:drug effects* / Q000378:metabolism*; D019821:Simvastatin / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects; D019745:cis-trans-Isomerases / Q000235:genetics; D000099178:Retinoid Isomerohydrolase; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
chemical_list: D053399:Apolipoproteins D; D002784:Cholesterol; D006845:Hydrocarbons, Fluorinated; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D019821:Simvastatin; D013449:Sulfonamides; D044767:Ubiquitin-Protein Ligases; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase; C423915:T0901317; D005466:Fluorocarbons; D000096926:Benzenesulfonamides; C542022:Mylip protein, mouse
keywords: 3-hydroxy-3-methyl-glutaryl-CoA reductase; RPE65; age-related macular degeneration; cytochrome P450; liver X receptor; posttranslational regulation; sterol-regulatory element binding protein; transcriptional regulation