A Review and Update on the Molecular Basis of Pathogenesis of Sorsby Fundus Dystrophy
Sorsby fundus dystrophy (SFD) is a rare autosomal dominant macular degeneration characterized by abnormal thickening of Bruch’s membrane (BM) leading to macular atrophy and choroidal neovascularization (CNV). SFD is caused by mutations in the gene encoding the tissue inhibitor of metalloproteinase-3 (TIMP3), a multifunctional protein component of BM. Disturbed homeostasis in extracellular matrix (ECM) remodeling is likely involved in SFD pathology. Here, we summarize the current findings on the mechanism(s) by which mutant TIMP3 causes the phenotypical expression of SFD. In addition, the association between SFD and complex age-related macular degeneration (AMD) is discussed.
KeywordsSorsby fundus dystrophy Choroidal neovascularization Bruch’s membrane TIMP3 Extracellular matrix Angiogenesis VEGF AMD
- Ebrahem Q, Qi J, Sugimoto M et al. (2011) Increased neovascularization in mice lacking tissue inhibitor of metalloproteinases-3. Invest Ophthalmol Vis Sci 52:6117-6123Google Scholar
- Kamei M, Hollyfield JG (1999). Invest Ophthalmol Vis Sci 40:2367–2375Google Scholar
- Klenotic PA, Munier FL, Marmorstein LY et al (2004) Tissue inhibitor of metalloproteinases-3 (TIMP-3) is a binding partner of epithelial growth factor-containing fibulin-like extracellular matrix protein 1 (EFEMP1). Implications for macular degenerations. J Biol Chem 279:30469–30473PubMedCrossRefGoogle Scholar
- Sorsby A, Mason MEJ, Gardner N (1949) A fundus dystrophy with unusual features (late onset and dominant inheritance of a central retinal lesion showing oedema, haemorrhage and exudates developing into generalised choroidal atrophy with massive pigment proliferation). Br J Ophthalmol 33: 67–97PubMedCrossRefGoogle Scholar