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New Study Says Inflammation May Cause AMD
Bacterium present in eyes with 'wet' age-related
macular degeneration
Nov. 7, 2005 Chlamydia pneumoniae, a bacterium
linked to heart disease and capable of causing chronic inflammation, was
present in the diseased eye tissue of five out of nine people with
neovascular, or "wet," age-related macular degeneration (AMD), in a
recent study. It was not, however, found in the eyes of more than 20
individuals without AMD, providing more evidence that this disease may
be caused by inflammation. AMD is the leading cause of blindness in baby
boomers and senior citizens over age 55.
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Researchers at the Massachusetts Eye and Ear
Infirmary (MEEI) conducted the study published in the November issue of
Graefe's Archive for Clinical and Experimental Ophthalmology.
The majority of vision loss is due to neovascular
AMD, the advanced form of the disease characterized by the formation of
blood vessels in the macula, the center part of the eye's retina. These
blood vessels often leak, thus giving neovascular AMD the name of "wet"
AMD.
Researchers at the MEEI and Harvard Medical School
(HMS) examined nine wet AMD membranes for the presence of C. pneumoniae
and also determined whether this pathogen can change the function of eye
cells in ways that can cause wet AMD. They found C. pneumoniae in the
eyes of five out of the nine patients with wet AMD. They also tested
tissue from more than 20 people who did not have AMD and did not find C.
pneumoniae in any of these normal eye tissues.
"The paper showed that C. pneumoniae is capable of
modifying the function of important cell types involved in regulating
normal eye function," said lead author Murat Kalayoglu, MD, PhD. "We
found that C. pneumoniae infection led to increased production of
vascular endothelial growth factor (VEGF), the key protein involved in
wet AMD. That C. pneumoniae infection of human eye cell types increases
VEGF production is therefore significant and could explain in part why
VEGF levels are increased in many people with wet AMD." Kalayoglu is an
HMS research fellow in ophthalmology at MEEI.
Most of the new medications either marketed or
being developed to treat wet AMD, such as Macugen (EyeTech
Pharmaceuticals) and Lucentis (Genetech) block VEGF.
The study comes at a time of great interest in
inflammatory mediators of AMD. Over the past seven months, a flurry of
high-impact papers have shown, in aggregate, that nearly 50 percent of
AMD can be explained by variations in a gene called Complement Factor H
(CFH). This gene makes a protein that regulates the immune and
inflammatory responses of the body.
"Our hypothesis is that C. pneumoniae may be the
key link between CFH and AMD," Kalayoglu said. "That is, patients with
CFH variations may be particularly susceptible to the damaging effects
of chronic infection, and an infectious organism like C. pneumoniae may
be particularly effective in accelerating inflammation and driving
progression of AMD in these patients."
Kalayoglu and colleagues are currently
collaborating with CFH researchers to study this hypothesis. "It may be
possible to stop or reverse progression of AMD by identifying
susceptible patients by diagnostic testing, and then treating these
susceptible patients. Although C. pneumoniae is a bacterium that might
respond to some antibiotics, much more work needs to be done before
considering antibiotic therapy for AMD," he said.
"This is an important study suggesting that
infection with C. pneumoniae may be a critical link between a genetic
predisposition to AMD and actual progression to disease," said Gerald I.
Byrne, Ph.D., professor and chairman of the Department of Molecular
Sciences University of Tennessee Health Sciences Center. "This is yet
another example of how an infection may unexpectedly contribute to a
chronic disease. Certainly the association of C. pneumoniae with heart
disease sets the stage for this pathogen's involvement in other chronic
conditions. This work is, in some ways, reminiscent of studies done more
than 15 years ago on infections and ulcers. Those studies were viewed
with skepticism, but Drs. Marshal and Warren, the researchers who
pioneered that work received the Nobel Prize this year."
The Graefe's paper builds on data from the same
group that showed, for the first time, that an infectious agent is
associated with AMD by epidemiological studies (Archives of
Ophthalmology, April 2003).
About the source
Massachusetts Eye And Ear Infirmary
http://www.meei.harvard.edu
Founded in 1824, MEEI is an international center for treatment and
research and a teaching hospital of Harvard Medical School. For more
information, call 617-573-3700 or TDD 617-523-5498.
Harvard Medical School
http://hms.harvard.edu/
Harvard Medical School has more than 6,000 full-time faculty working in
eight academic departments based at the School's Boston quadrangle or in
one of 47 academic departments at 18 Harvard teaching hospitals and
research institutes. Those Harvard hospitals and research institutions
include Beth Israel Deaconess Medical Center, Brigham and Women's
Hospital, Cambridge Health Alliance, the CBR Institute for Biomedical
Research, Children's Hospital Boston, Dana-Farber Cancer Institute,
Forsyth Institute, Harvard Pilgrim Health Care, Joslin Diabetes Center,
Judge Baker Children's Center, Massachusetts Eye and Ear Infirmary,
Massachusetts General Hospital, Massachusetts Mental Health Center,
McLean Hospital, Mount Auburn Hospital, Schepens Eye Research Institute,
Spaulding Rehabilitation Hospital, and VA Boston Healthcare System.
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