Abstract
Sorsby's fundus dystrophy (SFD) is an autosomal dominant retinal degeneration caused by mutations in the tissue inhibitor of metalloproteinases-3 (TIMP3) gene. Mechanisms of the visual loss in SFD, however, remain unknown. In a SFD family with a novel TIMP3 point mutation, we tested a hypothesis that their night blindness is due to a chronic deprivation of vitamin A at the level of the photoreceptors caused by a thickened membrane barrier between the photoreceptor layer and its blood supply. Vitamin A at 50,000 IU/d was administered orally. Within a week, the night blindness disappeared in patients at early stages of disease. Nutritional night blindness is thus part of the pathophysiology of this genetic disease and vitamin A supplementation can lead to dramatic restoration of photoreceptor function.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adult
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Bruch Membrane / drug effects
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Bruch Membrane / metabolism
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Bruch Membrane / pathology*
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DNA Mutational Analysis
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Diffusion
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Eye Proteins / genetics*
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Female
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Fundus Oculi*
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Humans
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Male
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Middle Aged
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Night Blindness / drug therapy*
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Night Blindness / etiology
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Night Blindness / metabolism
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Night Blindness / pathology
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Pedigree
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Point Mutation
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Polymorphism, Single-Stranded Conformational
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Proteins / genetics*
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Retinal Degeneration / complications*
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Retinal Degeneration / genetics
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Retinal Degeneration / metabolism
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Retinal Degeneration / pathology
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Retinal Rod Photoreceptor Cells / blood supply*
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Scotoma / drug therapy
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Scotoma / etiology
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Tissue Inhibitor of Metalloproteinase-3
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Vitamin A / administration & dosage
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Vitamin A / pharmacokinetics
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Vitamin A / therapeutic use*
Substances
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Eye Proteins
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Proteins
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Tissue Inhibitor of Metalloproteinase-3
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Vitamin A