Researchers spot another blinding gene.

Investigators have scored again in their efforts to understand the genetic causes of macular dystrophies, eye disorders that damage the central portion of the retina. These diseases include age-related macular degeneration, a leading cause of blindness.

Because the disease strikes late in life, getting enough family members together for a genetics study can prove difficult, says Edwin M. Stone of the University of Iowa in Iowa City. Parents have usually died by the time the disorder strikes their children. So to understand the genetics of the eye disorder, researchers often study closely related diseases.

In this latest discovery, scientists find that two mutations on the gene for an enzyme called tissue inhibitor of metalloproteinases-3 (TIMP3) may lead to Sorsby's fundus dystrophy (SFD), which usually strikes adults before age 50, report Bernhard H. F. Weber of the Julius Maximilians University in Wurzburg, Germany, and his colleagues.

"It's a very, very significant contribution," says Stone, who coauthored earlier studies describing a gene associated with a similar macular disorder (SN: 7/18/92, p. 37).

Weber's team found different mutations in TIMP3 in two unrelated families with SFD. The investigators could not detect mutations in healthy family members or in 176 other volunteers.

"To our knowledge, this is the first report providing strong evidence that mutations in a member of the TIMP gene family are causative of a degenerative human disease, namely SFD," Weber's group reports in the December NATURE GENETICS.

The TIMP3 mutations may promote excessive growth of blood vessels through Bruch's membrane, which lies below the retina, they speculate. As a result, the membrane thickens or bleeds, disrupting vision. How the mutations cause this growth remains a mystery, but it occurs more often in SFD patients than in those with other macular dystrophies.

Researchers don't know whether these findings will ever lead to gene therapy for macular disorders. Stone argues that too many people develop macular degeneration for the disease to be a candidate for gene therapy.

"You're probably not going to go in there and replace the TIMP3 gene in the retina in a bunch of 70-year-olds. What you're going to do, hopefully, is understand why the blood vessels [grow excessively] and come up with some drug or something that can shut that down."

The retinal degeneration-slow-peripherin gene, the only other specific gene implicated in macular dystrophy, helps maintain the structure of the photoreceptors in the eyes. Some mutations in the gene appear to lead to a degenerative retinal condition known as retinitis pigmentosa, while others cause macular disease, Stone says.

"It remains to be shown ... how exactly all of these mutations cause these diseases.... That's going to take a whole bunch more work," Stone points out.