Can Vitamin A be Improved to Prevent Blindness due to Age-Related Macular Degeneration, Stargardt Disease and Other Retinal Dystrophies?

Adv Exp Med Biol. 2016;854:355-61. doi: 10.1007/978-3-319-17121-0_47.


We discuss how an imperfect visual cycle results in the formation of vitamin A dimers, thought to be involved in the pathogenesis of various retinal diseases, and summarize how slowing vitamin A dimerization has been a therapeutic target of interest to prevent blindness. To elucidate the molecular mechanism of vitamin A dimerization, an alternative form of vitamin A, one that forms dimers more slowly yet maneuvers effortlessly through the visual cycle, was developed. Such a vitamin A, reinforced with deuterium (C20-D3-vitamin A), can be used as a non-disruptive tool to understand the contribution of vitamin A dimers to vision loss. Eventually, C20-D3-vitamin A could become a disease-modifying therapy to slow or stop vision loss associated with dry age-related macular degeneration (AMD), Stargardt disease and retinal diseases marked by such vitamin A dimers. Human clinical trials of C20-D3-vitamin A (ALK-001) are underway.

Keywords: A2E; ABCA4; ALK-001; AMD; Age-related macular degeneration; Bisretinoids; C20-D3-vitamin A; Lipofuscin; Retinal dystrophies; Retinaldehyde; Stargardt; Visual cycle; Vitamin A; Vitamin A dimer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blindness / etiology
  • Blindness / prevention & control*
  • Clinical Trials as Topic
  • Deuterium / chemistry
  • Dimerization
  • Humans
  • Macular Degeneration / complications
  • Macular Degeneration / congenital*
  • Macular Degeneration / prevention & control*
  • Models, Chemical
  • Molecular Conformation / drug effects
  • Molecular Structure
  • Phenyl Ethers / therapeutic use
  • Propanolamines / therapeutic use
  • Retinal Dystrophies / complications
  • Retinal Dystrophies / prevention & control*
  • Stargardt Disease
  • Vitamin A / chemistry
  • Vitamin A / therapeutic use*
  • Vitamins / chemistry
  • Vitamins / therapeutic use


  • Phenyl Ethers
  • Propanolamines
  • Vitamins
  • emixustat
  • Vitamin A
  • Deuterium

Supplementary concepts

  • Stargardt disease 1