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
- Research Support, Non-U.S. Gov't
- Research Support, U.S. Gov't, P.H.S.
MeSH terms
- Adult
- Bruch Membrane / drug effects
- Bruch Membrane / metabolism
- Bruch Membrane / pathology*
- DNA Mutational Analysis
- Diffusion
- Eye Proteins / genetics*
- Female
- Fundus Oculi*
- Humans
- Male
- Middle Aged
- Night Blindness / drug therapy*
- Night Blindness / etiology
- Night Blindness / metabolism
- Night Blindness / pathology
- Pedigree
- Point Mutation
- Polymorphism, Single-Stranded Conformational
- Proteins / genetics*
- Retinal Degeneration / complications*
- Retinal Degeneration / genetics
- Retinal Degeneration / metabolism
- Retinal Degeneration / pathology
- Retinal Rod Photoreceptor Cells / blood supply*
- Scotoma / drug therapy
- Scotoma / etiology
- Tissue Inhibitor of Metalloproteinase-3
- Vitamin A / administration & dosage
- Vitamin A / pharmacokinetics
- Vitamin A / therapeutic use*
Substances
- Eye Proteins
- Proteins
- Tissue Inhibitor of Metalloproteinase-3
- Vitamin A