Iowa Eye Association News Oct. 2004. Series 2, no. 39.

University of Iowa Hospitals & Clinics Department of Ophthalmology and Visual Sciences

NOTE: This page is for archival purposes only and may contain information that is outdated.

Genetic Finding Has Implications
for Preventing Blindness

In the July 22, 2004, issue of the New England Journal of Medicine, Edwin M. Stone, M.D., Ph.D., and colleagues reported that a gene called fibulin 5 is associated with 1.7 percent of age-related macular degeneration (AMD) cases. The finding could help researchers develop preventive treatments for people affected by this particular form of AMD — at least 100,000 in the United States alone. The discovery may also point the way to preventing vision loss in millions of people affected by the many other forms of AMD.

In the current study, the team searched for variations in five other fibulin genes in people with AMD and people without the disease. The team found an altered fibulin 5 gene in seven of the 402 (1.7 percent) people with macular degeneration but not in any of the 429 controls.

“While 1.7 percent may seem insignificant, the 100,000 to 150,000 people it represents in the United States actually is a larger group of people than all those with Hodgkins disease or sickle cell anemia,” Stone said.

Age-related macular degeneration is really a large group of diseases, perhaps as many as 50. Thus, it is likely that researchers will eventually find numerous genetic clues involved in the various forms of this common disease. “There remain many different genes and also many environmental influences to find and study,” says Stone.

“Once we understand the mechanisms sufficiently, we think that it will be possible to intervene perhaps when someone is 40 years old and arrest or slow the disease before it causes damage. We are fortunate that genetics play a major role in AMD because if it had purely environmental causes, we’d probably never figure it out,” he added.

Because of the variety of causes, no single drug or treatment is likely to work for all people with macular degeneration. However, the fibulin 5 gene finding is one of the genetic clues that clinicians eventually could use to determine the form of macular degeneration for which a patient is at risk and then choose the best prevention.

“The retina is such a delicate, fragile organ that you can’t take a little piece of it from a living patient to find out what’s wrong,” Stone explained. “For decades, ophthalmologists have been able to look inside the eye and see the drusen but they have not been able to determine biochemically what is wrong with the eye unless patients donate their eyes for research after their death. Molecular genetics is a very powerful way for us to understand disease when tissue samples are scarce,” Stone added.

In addition to Stone, major contributors to the paper included Terry A. Braun, Ph.D., assistant professor of ophthalmology and biomedical engineering; Thomas L. Casavant, Ph.D., UI professor of electrical and computer engineering and biomedical engineering; Stephen R. Russell, M.D., associate professor of ophthalmology and service director of Vitreoretinal Disease and Surgery; and Val C. Sheffield, M.D., Ph.D., UI professor of pediatrics and also a Howard Hughes Medical Investigator.

Reference

Stone EM, Braun TA, Russell SR, Kuehn MH, Lotery A, Moore PA, Eastman CG, Casavant TL, Sheffield VC. Missense Variations in the Fibulin 5 Gene and Age-Related Macular Degeneration. New England Journal of Medicine. 2004;351:346-353.

Visit the CMD website