ECM in Sight

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Science  06 Aug 2004:
Vol. 305, Issue 5685, pp. 754
DOI: 10.1126/science.305.5685.754a

More than 10% of elderly Caucasians in the United States suffer from age-related macular degeneration (AMD), an eye disorder that gradually destroys central vision and is characterized by the breakdown of light-sensing retinal cells. Previous genetic studies of an inherited form of AMD and of a macular degenerative disease resembling AMD (Malattia Leventinese) have implicated two glycoproteins—fibulin-6 and fibulin-3, respectively—that are thought to participate in the assembly and stabilization of the extracellular matrix (ECM).

Two new studies underscore the importance of the fibulin protein family and the ECM in the pathogenesis of macular degeneration. Klenotic et al. find that fibulin-3 binds strongly in vivo to tissue inhibitor of metalloproteinases-3 (TIMP-3), a protein that suppresses ECM degradation and is itself mutated in a third type of inherited macular degeneration (Sorsby fundus dystrophy). Stone et al. report that about 2% of patients with sporadic AMD have missense mutations in the gene encoding fibulin-5. All of these mutations may disrupt the integrity or function of Bruch's membrane, a region of the eye where abnormal extracellular deposits (drusen) accumulate in patients with macular degeneration. — PAK

J. Biol. Chem. 279, 30469 (2004); N. Engl. J. Med. 351, 346 (2004).

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