By Gail Gallessich

Alterations in a gene involved in the body’s immune system dramatically increase the likelihood of developing a blinding disease late in life, according to new findings by an international team of scientists. Similar alterations in the same gene were found to be associated with a rare and often fatal kidney disease.

The blinding disease, age-related macular degeneration (AMD), is characterized by a progressive loss of central vision due to a buildup of drusen, which are protein and cholesterol deposits in the eye. This leads to degeneration of the macula, a region of the retina in the back of the eye.

AMD is the leading cause of irreversible blindness in individuals over the age of 60. No cure currently exists, and available therapeutics treat only the vascular complications that occur in 10 to 15 percent of AMD patients.

The genetic linkage results, which represent the culmination of studies conducted over several years, were published earlier this month in the online edition of the Proceedings of the National Academy of Sciences. Two coauthors are from UC Santa Barbara.

Don Anderson, director of the Center for the Study of Macular Degeneration in UCSB’s Neuroscience Research Institute, and Lincoln Johnson, associate director of the center, coauthored the article. Anderson and Johnson worked with lead author Gregory Hageman and his colleagues at the University of Iowa Carver College of Medicine, and geneticist Rando Allikmets at Columbia University. Other collaborating scientists included Richard Smith and Giuliana Silvestri of Queens University, Belfast, Northern Ireland, and Michael Dean of the National Cancer Institute.

Together the scientists discovered that a pattern of inherited flaws in the gene called Factor H (which regulates the body’s immune system response against infection by bacteria, viruses, and other microbes) dramatically increase one’s susceptibility to AMD late in life. Additionally, the individuals most susceptible to AMD, are also susceptible to a rare, fatal kidney disease called membranoproliferative glomerulonephritis, type II (MPGN II).

The first hint of a possible link between AMD and MPGN II came when it was discovered earlier that individuals with MPGN II also develop ocular drusen, but at a much earlier age. When combined with triggering events, such as infection, the result was local tissue damage, particularly at locations in the kidney and in the macula, which have similarities in both structure and function.

Analyzing the molecular composition of drusen, it became evident that many of the proteins were related to those in what scientists term the “complement system.” This is a part of the body’s immune system that recognizes and kills invading microorganisms.

Stimulated by inflammation, the complement system dispatches proteins to destroy the invaders. But if the Factor H gene is faulty, the complement proteins may destroy some of the body’s own tissue.

The molecular composition of drusen suggested that AMD, like many other age-related diseases such as Alzheimer’s disease and atherosclerosis, had an inflammatory component, said Anderson. “Now that the genetic evidence for Factor H involvement is in, it looks like the inflammation model of AMD is correct.”

Added Hageman: “The genetic key was that people with MPGN II and people with AMD had both already been linked to a region on chromosome 1.”

The new genetic findings, researchers believe, will lead to the rapid development of early diagnostic tests for AMD, and new therapeutic approaches that will benefit a much larger proportion of the early AMD patient population.