Chlamydia infection connected to AMD

Investigators explore bacterial tie to AMD

A new study suggests that age-related macular degeneration (AMD) may be linked in some cases to the bacterium Chlamydia pneumoniae. Investigators, led by Murat V. Kalayoglu, M.D., Ph.D., found C. pneumoniae in approximately 50% of AMD cases, but not in eyes without AMD, according to study results published in the November 2005 issue of Graefe’s Archive for Clinical Experimental Ophthalmology.
C. pneumoniae is an all too common ailment, particularly in the elderly population. “In patients in their 70s or 80s, testing by antibodies suggests that over 70% of individuals at some point have been infected with C. pneumoniae,” said Dr. Kalayoglu, Massachusetts Eye and Ear Infirmary, Boston.
Unlike its sexually transmitted counterpart, Chlamydia trachomatis, C. pneumoniae is spread through the air.
“It is transmitted through respiratory air droplets and causes a low-grade atypical walking pneumonia,” Dr. Kalayoglu said. “About 15% of patients with community acquired pneumonia have it because of Chlamydia pneumoniae infection.”

Inflammatory link

Multiple Chlamydia pneumoniae
inclusions within an infected human
retinal pigmented epithelium (RPE)
cell.
Source: Murat V. Kalayoglu, M.D.,
Ph.D.

The suspicion has long been that C. pneumoniae, which can cause chronic inflammation, may be spurring diseases such as heart disease. In fact, Dr. Kalayoglu’s original work in the field was centered on identifying specific ways in which the organism could initiate and promote the development of atherosclerosis—the leading cause of coronary artery disease.
“The organism is strongly associated with heart disease and that kind of evidence began to get me interested in thinking about other types of diseases with which Chlamydia pneumoniae could be associated,” he said. “The one disease in the eye that I thought had many risk factors in common with atherosclerosis was macular degeneration.”
He noted common risk factors such as high blood pressure, smoking, advanced age, as well as certain types of oxidized lipids that may be associated with both conditions.
“They also share similar types of disease processes,” Dr. Kalayoglu said. “There is more and more evidence that macular degeneration is an inflammatory disease and certainly 15 years ago there was a paradigm shift in heart disease indicating that atherosclerosis is also inflammatory.”

Studying C. pneumoniae

Dr. Kalayoglu and fellow investigators launched the study on C. pneumoniae to see if it might be related to AMD. The study included nine choroidal neovascular membranes from patients with typical AMD and 22 other specimens from eyes that did not demonstrate any evidence of the disorder.
“We were able to detect Chlamydia pneumoniae from a subset of patients,” Dr. Kalayoglu said. Five out of nine patients with AMD that had choroidal neovascular membranes were also identified as having C. pneumoniae. No evidence of C. pneumoniae was found in any of the 22 other eyes that showed no signs of AMD.
Investigators also found that C. pneumoniae infection led to increased production of vascular endothelial growth factor (VEGF). The fact that VEGF levels are elevated in patients with AMD may in part be linked to C. pneumoniae infections, he believes.
However, Dr. Kalayoglu makes plain that the organism alone is not enough to cause AMD. “There is plenty of evidence that the organism is not sufficient in and of itself to initiate either atherosclerosis or, age related macular degeneration,” he said.
He points to animals with a genetic propensity for atherosclerosis that have been raised in an infection-free environment that still go on to develop heart disease. It appears as if a certain susceptibility is needed.
“I think that C. pneumoniae could serve as a trigger in accelerating or promoting the development of age-related macular degeneration in a subset of patients who are infected,” Dr. Kalayoglu said. “Not every patient is going to be affected. You either have to be unlucky, or you have to have a certain susceptibility, or both.”
Although the connection found in the study with C. pneumoniae was to wet macular degeneration, Dr. Kalayoglu believes that the infection is likely linked to both diseases. Chlamydia infections tend to be long-standing low-grade chronic ones, he pointed out.
“One way to look at this is the organism may be around for many years and promotes the development of mild dry to advanced dry and then maybe from advanced dry to wet,” he said. “Or, the second way to consider is that the patient just happens to get infected when they’re in the advanced dry stage and this promotes their converting from advanced dry to wet.”

Antibiotic use premature

While use of antibiotics may eventually be an attractive option in treating some AMD patients it is currently a very premature one, Dr. Kalayoglu said.
“I certainly don’t think that treating everyone down the line with antibiotics makes any sense,” he said. “You have to find the appropriate risk equation, where you have to be able to carefully identify a patient who not only is infected but who has the disease and the kind of disease that may respond to treatment.”
“At this point I would strongly caution any practitioner not to use any antibiotics for the treatment of macular degeneration,” Dr. Kalayoglu said. “Currently no clinical data support any role of any antibiotic treatment in macular degeneration, especially given the data about antibiotic resistance.”
Efforts now need to be focused on further study, Dr. Kalayoglu believes. “We need to focus efforts on the appropriate kinds of studies to solidify the link between the organism and age-related macular degeneration rather than focusing efforts at this point on the treatment of the disease with antibiotics,” he said.

Editors’ note: Dr. Kalayoglu has an appointment at the Massachusetts Eye and Ear Infirmary, Boston, and has pending patent applications relating to infection and AMD.

Contact Information
Kalayoglu: 408-394-6380, murat@sloan.mit.edu