Bacterium present in eyes with ’wet’ age-related macular degeneration

Researchers at the Massachusetts Eye and Ear Infirmary (MEEI) have found that 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). However, it was not found in the eyes of more than 20 individuals without AMD, providing more evidence that this disease may be caused by inflammation. The study is described in the November issue of Graefe’s Archive for Clinical and Experimental Ophthalmology.

AMD is the leading cause of blindness in Americans over the age of 55. 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).