System, Eye Disease Linked
||UCSB Neuroscience Institute
researchers Lincoln Johnson, seated, and Don Anderson were part
of a team that discovered a link between inflammation and a
genetic flaw associated with age-related macular degeneration.
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.