title: C20-D3-vitamin A slows lipofuscin accumulation and electrophysiological retinal degeneration in a mouse model of Stargardt disease.
abstract: Stargardt disease, also known as juvenile macular degeneration, occurs in approximately one in 10,000 people and results from genetic defects in the ABCA4 gene. The disease is characterized by premature accumulation of lipofuscin in the retinal pigment epithelium (RPE) of the eye and by vision loss. No cure or treatment is available. Although lipofuscin is considered a hallmark of Stargardt disease, its mechanism of formation and its role in disease pathogenesis are poorly understood. In this work we investigated the effects of long-term administration of deuterium-enriched vitamin A, C20-D(3)-vitamin A, on RPE lipofuscin deposition and eye function in a mouse model of Stargardt's disease. Results support the notion that lipofuscin forms partly as a result of the aberrant reactivity of vitamin A through the formation of vitamin A dimers, provide evidence that preventing vitamin A dimerization may slow disease related, retinal physiological changes and perhaps vision loss and suggest that administration of C20-D(3)-vitamin A may be a potential clinical strategy to ameliorate clinical symptoms resulting from ABCA4 genetic defects.
authors.affiliation: From the Department of Ophthalmology, Columbia University Medical Center, New York, New York 10032.
authors.forename: Li
authors.initials: L
authors.lastname: Ma
authors.affiliation: From the Department of Ophthalmology, Columbia University Medical Center, New York, New York 10032.
authors.forename: Yardana
authors.initials: Y
authors.lastname: Kaufman
authors.affiliation: From the Department of Ophthalmology, Columbia University Medical Center, New York, New York 10032.
authors.forename: Junhua
authors.initials: J
authors.lastname: Zhang
authors.affiliation: From the Department of Ophthalmology, Columbia University Medical Center, New York, New York 10032. Electronic address: iw2101@columbia.edu.
authors.forename: Ilyas
authors.initials: I
authors.lastname: Washington
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000818:Animals; D003903:Deuterium; D019281:Dimerization; D004195:Disease Models, Animal; D006801:Humans; D008062:Lipofuscin / Q000096:biosynthesis* / Q000235:genetics; D008268:Macular Degeneration / Q000151:congenital / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D012162:Retinal Degeneration / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D000080362:Stargardt Disease; D014801:Vitamin A / Q000737:chemistry / Q000494:pharmacology*; D014815:Vitamins / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D018528:ATP-Binding Cassette Transporters; C512841:Abca4 protein, mouse; D008062:Lipofuscin; D014815:Vitamins; D014801:Vitamin A; D003903:Deuterium