title: Partial rescue of retinal function and sterol steady-state in a rat model of Smith-Lemli-Opitz syndrome.
abstract: The Smith-Lemli-Opitz syndrome (SLOS) is the first-described in a growing family of hereditary defects in cholesterol biosynthesis, and presents with a spectrum of serious abnormalities, including multiple dysmorphologies, failure to thrive, cognitive and behavioral impairments, and retinopathy. Using a pharmacologically induced rat model of SLOS that exhibits key hallmarks of the disease, including progressive retinal degeneration and dysfunction, we show that a high-cholesterol diet can substantially correct abnormalities in retinal sterol composition, with concomitant improvement of visual function, particularly within the cone pathway. Although histologic degeneration still occurred, a high-cholesterol diet reduced the number of pyknotic photoreceptor nuclei, relative to animals on a cholesterol-free diet. These findings demonstrate that cholesterol readily crosses the blood-retina barrier (unlike the blood-brain barrier) and suggest that cholesterol supplementation may be efficacious in treating SLOS-associated retinopathy.
authors.affiliation: Department of Ophthalmology, Saint Louis University School of Medicine, St. Louis, Missouri 63104, USA. Fliesler@slu.edu
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Fliesler
authors.forename: Dana K
authors.initials: DK
authors.lastname: Vaughan
authors.forename: Erin C
authors.initials: EC
authors.lastname: Jenewein
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Richards
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Nagel
authors.forename: Neal S
authors.initials: NS
authors.lastname: Peachey
mesh_terms: D000818:Animals; D002791:Cholesterol, Dietary / Q000008:administration & dosage / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D020419:Photoreceptor Cells, Vertebrate / Q000473:pathology / Q000502:physiology; D011247:Pregnancy; D051381:Rats; D012160:Retina / Q000473:pathology / Q000503:physiopathology*; D019082:Smith-Lemli-Opitz Syndrome / Q000139:chemically induced / Q000178:diet therapy* / Q000378:metabolism / Q000503:physiopathology*; D013261:Sterols / Q000378:metabolism*; D001371:trans-1,4-Bis(2-chlorobenzaminomethyl)cyclohexane Dihydrochloride / Q000633:toxicity
chemical_list: D002791:Cholesterol, Dietary; D013261:Sterols; D001371:trans-1,4-Bis(2-chlorobenzaminomethyl)cyclohexane Dihydrochloride