title: Deuterium enrichment of vitamin A at the C20 position slows the formation of detrimental vitamin A dimers in wild-type rodents.
abstract: Degenerative eye diseases are the most common causes of untreatable blindness. Accumulation of lipofuscin (granular deposits) in the retinal pigment epithelium (RPE) is a hallmark of major degenerative eye diseases such as Stargardt disease, Best disease, and age-related macular degeneration. The intrinsic reactivity of vitamin A leads to its dimerization and to the formation of pigments such as A2E, and is believed to play a key role in the formation of ocular lipofuscin. We sought a clinically pragmatic method to slow vitamin A dimerization as a means to elucidate the pathogenesis of macular degenerations and to develop a therapeutic intervention. We prepared vitamin A enriched with the stable isotope deuterium at carbon twenty (C20-D(3)-vitamin A). Results showed that dimerization of deuterium-enriched vitamin A was considerably slower than that of vitamin A at natural abundance as measured in vitro. Administration of C20-D(3)-vitamin A to wild-type rodents with no obvious genetic defects in vitamin A processing, slowed A2E biosynthesis. This study elucidates the mechanism of A2E biosynthesis and suggests that administration of C20-D(3)-vitamin A may be a viable, long-term approach to retard vitamin A dimerization and by extension, may slow lipofuscin deposition and the progression of common degenerative eye diseases.
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: Li
authors.initials: L
authors.lastname: Ma
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: D000818:Animals; D003903:Deuterium / Q000737:chemistry*; D019281:Dimerization; D008062:Lipofuscin / Q000096:biosynthesis*; D008268:Macular Degeneration / Q000378:metabolism*; D051379:Mice; D008813:Mice, Inbred ICR; D011726:Pyridinium Compounds; D012176:Retinoids / Q000096:biosynthesis*; D014801:Vitamin A / Q000737:chemistry / Q000494:pharmacology; D014815:Vitamins / Q000737:chemistry / Q000494:pharmacology
chemical_list: C112040:A2-E (N-retinylidene-N-retinylethanolamine); D008062:Lipofuscin; D011726:Pyridinium Compounds; D012176:Retinoids; D014815:Vitamins; D014801:Vitamin A; D003903:Deuterium