Sorsby's fundus dystrophy: what does TIMP3 tell us about general mechanisms underlying macular degeneration?

INTRODUCTION: Mutations in tissue inhibitor of metalloproteinases-3 (TIMP3) gene result in the rare autosomal dominant disease Sorsby's fundus dystrophy (SFD), which shows striking similarities to age-related macular degeneration (ARMD). METHODS: Current research is reviewed and suggests that these mutations result in the accumulation of TIMP3 in Bruch's membrane resulting in decreased turnover of the extracellular matrix and consequent thickening of Bruch's membrane. DNA analysis of ARMD patients has failed to show any significant mutations in the coding-regions of TIMP3. However, this should not be taken to imply that TIMP3 is not affected in the disease, as another possibility is that levels of TIMP3 might be elevated by other mechanisms. CONCLUSION: The finding that TIMP3 levels are elevated in simplex retinitis pigmentosa in the absence of coding mutations begs for a revaluation of its role in other retinal conditions such as ARMD.