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.
Stargardt Age-related macular degeneration AMD Retinal dystrophies ABCA4 Vitamin A Retinaldehyde ALK-001 C20-D3-vitamin A Bisretinoids Vitamin A dimer A2E Lipofuscin Visual cycle
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We thank the U.S. National Institutes of Health (1R01EY021207 and 5P30EY019007) and Research to Prevent Blindness (RPB) Inc., New York.
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