Serological Association Between Chlamydia pneumoniae Infection and Age-Related Macular Degeneration

Abstract

Background: Age-related macular degeneration (ARMD) is a leading cause of blindness in the United States, but the mechanisms that initiate and promote the disease remain ill defined. There are several risk factors that ARMD shares with atherosclerosis, and these diseases may have similar pathogenic mechanisms that involve inflammation. Chlamydia pneumoniae, a prokaryotic pathogen that causes chronic inflammation is now emerging as a risk factor in the development of cardiovascular diseases. It is therefore plausible that this microorganism also contributes to the pathogenesis of ARMD. Methods: To examine if C pneumoniae infection is associated with ARMD, serum samples from 25 consecutive patients with ARMD and from 18 without the disease were collected and assayed for the presence of the antibodies to C pneumoniae elementary bodies, Chla-mydia trachomatis heat shock protein 60 (cHsp60), C trachomatis heat shock protein 10 (cHsp10), Escherichia coli GroEL, and E coli GroES. Results: A serological association was found between ARMD and anti-C pneumoniae antibodies (P =.047) but not between ARMD and the anti-C trachomatis or anti-E coli heat shock protein antibodies. The association remained statistically significant after adjusting for age and smoking, both established risk factors for ARMD. Conclusions: These data indicate that C pneumoniae infection may be associated with ARMD. Further studies on larger cohorts of individuals are necessary to determine if this pathogen plays a role in the pathogenesis of ARMD.

Immunopathological aspects of age-related macular degeneration

“…Though further studies are needed, recent evidence suggests that prior C. pneumoniae infection might also be implicated in AMD pathogenesis [87][88][89][90][91]. Though further studies are warranted, prior studies suggest showing that C. pneumoniae infection activates the alternative complement pathway and promotes macrophage activation and recruitment suggest that the role of C. pneumoniae, if any, in AMD might intersect with one or more of the immunologic processes described here [94,95].…”

“…Specifically, several investigators have correlated prior Chlamydia pneumoniae, an intracellular pathogen that has been associated with inflammatory diseases such as atherosclerosis, with AMD. Two studies by Kalayoglu and Robman and their colleagues [87,88] demonstrated that serum antibodies for C. pneumoniae proteins are associated with increased risk of AMD development and progression. A later study by Kalayoglu et al reported that CNV specimens from AMD patients are significantly more likely to show evidence of C. pneumoniae by immunohistochemistry, when compared to non-AMD CNV and non-AMD eyes.…”

Inflammation, Complement Factor H, and Age-Related Macular Degeneration

“…49 Data from 2 small case control studies also showed an association with C. pneumoniae, but not other pathogens with AMD. 50,51 It was speculated that macrophages infected with C. pneumoniae may enter the circulatory system and spread to the choroid resulting in production of inflammatory cytokines such as tumor necrosis factor-α. It is possible that pathogen exposure is involved in advanced stages of AMD involving neovascularization of the choroid.…”

“…It is possible that pathogen exposure is involved in advanced stages of AMD involving neovascularization of the choroid. 50 However, in MESA, there were no relationships of 5 biomarkers of previous pathogen exposure, including C. pneumoniae, and prevalent early or late AMD and there was no apparent interaction with CFH status. This is consistent with findings from the Beaver Dam and Blue Mountains Eye studies.…”

The complement system and age-related macular degeneration

“…Chlamydia pneumoniae which is also an activator of complement system was recently implicated in the pathogenesis of AMD. 30 All these data are suggestive of the existence of multiple activators of complement in the RPE-choroid complex which mediate complement activation in AMD.…”