Macular degeneration results from wear and tear over the years in the center of the retina, and afflicts mainly the elderly. Genetics is suspected to be a factor in this degenerative disease; for instance, mutations in the gene encoding fibulin-3 contribute to an early-onset form. In the 22 July issue of New England Journal of Medicine, Edwin Stone et al. implicate mutations in a related gene, encoding fibulin-5, in late-onset disease.

Credit: Reprinted with permission of NEJM

The researchers sequenced six genes in the fibulin family and found missense mutations in the fibulin-5 gene in 7 of 402 patients with age-related macular degeneration. The mutations were not the same in each individual, but six mutations deviated from conserved sequences in several species. Many variations in the other fibulin genes were also found in the patients, although larger studies will be required to pin down a concrete association with disease.

Fibulin-5, an extracellular matrix protein, has binding sites for numerous basement membrane proteins and is required for polymerization of elastin. Elastin is a major component of a structure in the eye that gives rise to drusen, small bits of protein and lipid associated with this disease (Shown is an eye of a patient with a mutation in the gene for fibulin-5. Macula occupies central half of figure, optic nerve head is on right. Inset, arrow points to prominent drusen visible with fluorescein angiography.)