Researchers investigate link beween bacterium, AMD

March 15, 2006

Boston?Researchers at Massachusetts Eye & Ear Infirmary (MEEI), Boston, have discovered more evidence that inflammation plays a role in the pathogenesis of wet age-related macular degeneration (AMD). A team of investigators found Chlamydia pneumoniae, a pathogen capable of inducing chronic infection, in the diseased eye tissue of several patients with wet AMD, and the bacterium was not present in tissue from the eyes of a small group of patients without AMD.

"Our study was small and the numbers were small, but it's suggestive of an association between this bacterium and the neovascular form of macular degeneration," said Joan W. Miller, MD, Henry Willard Williams professor of ophthalmology, chief and chairman, department of ophthalmology, Harvard Medical School, MEEI. "Our work certainly supports what seems to be a growing body of evidence that inflammation plays a role in macular degeneration."

Investigators found C pneumoniae in the choroidal neovascular membrane (CNV) tissue of five of nine individuals with AMD but none of the 22 non-AMD specimens.

The membranes had been surgically extracted in what is now a very rare procedure, and the investigators were able to obtain only nine AMD CNV specimens from the MEEI pathology laboratory for immunohistochemistry (IHC) and polymerase chain reaction (PCR) analysis.

Detection of C pneumoniae

Four of the nine specimens showed evidence of C pneumoniae by IHC. C pneumoniae was also detected in two of the nine specimens by PCR. None of the 22 non-AMD samples showed evidence for the bacterium by either method of analysis.

Having attained antibody evidence of an indirect association and subsequently identifying the organism within the site of disease, a much more direct association, the investigators then wanted to tackle the question of whether the pathogen could cause the type of events that occur in wet macular degeneration.

"We determined that the organism was capable of infecting and multiplying within the relevant cell types, such as retinal pigment epithelial (RPE) cells and macrophages. We saw that you could infect these cells, and the organism could establish an active replicating life cycle within these cell types," Dr. Kalayoglu said.

Another objective was to learn whether the organism could increase the level of certain cytokines and angiogenic factors. "We determined that when you infect an RPE cell or macrophage, these cells have a modified function as a result of the infection and begin secreting increased levels of vascular endothelial growth factor (VEGF), interleukin-6, and interleukin-1 that are all associated with promoting the development of macular degeneration," he continued.

"When we put all this together, the idea from our end is to try to combine as many different lines of evidence as possible in order to strengthen further the association between infection and macular degeneration," Dr. Kalayoglu said.