C20-D3-vitamin A slows lipofuscin accumulation and electrophysiological retinal degeneration in a mouse model of Stargardt disease

J Biol Chem. 2011 Mar 11;286(10):7966-7974. doi: 10.1074/jbc.M110.178657. Epub 2010 Dec 14.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters / genetics
  • ATP-Binding Cassette Transporters / metabolism
  • Animals
  • Deuterium*
  • Dimerization
  • Disease Models, Animal
  • Humans
  • Lipofuscin / biosynthesis*
  • Lipofuscin / genetics
  • Macular Degeneration / congenital
  • Macular Degeneration / drug therapy
  • Macular Degeneration / genetics
  • Macular Degeneration / metabolism
  • Mice
  • Mice, Mutant Strains
  • Retinal Degeneration / drug therapy
  • Retinal Degeneration / genetics
  • Retinal Degeneration / metabolism*
  • Stargardt Disease
  • Vitamin A / chemistry
  • Vitamin A / pharmacology*
  • Vitamins / chemistry
  • Vitamins / pharmacology*


  • ATP-Binding Cassette Transporters
  • Abca4 protein, mouse
  • Lipofuscin
  • Vitamins
  • Vitamin A
  • Deuterium