Identification of Chlamydia pneumoniae within human choroidal neovascular membranes secondary to age-related macular degeneration.
Age-related macular degeneration (AMD) is a leading cause of blindness in the United States, and increasing evidence suggests that it is an inflammatory disease. The prokaryotic obligate intracellular pathogen Chlamydia pneumoniae is emerging as a novel risk factor in cardiovascular disease, and recent sero-epidemiological data suggest that C. pneumoniae infection is also associated with AMD. In this study, we examined choroidal neovascular membrane (CNV) tissue from patients with neovascular AMD for the presence of C. pneumoniae and determined whether the pathogen can dysregulate the function of key cell types in ways that can cause neovascular AMD. Nine CNV removed from patients with neovascular AMD were examined for the presence of C. pneumoniae by immunohistochemistry (IHC) and polymerase chain reaction (PCR); in addition, we performed PCR on nine non-AMD eyes, and IHC on five non-AMD CNV, seven non-AMD eyes, and one internal limiting membrane specimen. Finally, human monocyte-derived macrophages and retinal pigment epithelial (RPE) cells were exposed to C. pneumoniae and assayed in vitro for the production of pro-angiogenic immunomodulators (VEGF, IL-8, and MCP-1). C. pneumoniae was detected in four of nine AMD CNV by IHC and two of nine AMD CNV by PCR, induced VEGF production by human macrophages, and increased production of IL-8 and MCP-1 by RPE cells. In contrast, none of the 22 non-AMD specimens showed evidence for C. pneumoniae. These data indicate that a pathogen capable of inducing chronic inflammation and pro-angiogenic cytokines can be detected in some AMD CNV, and suggest that infection may contribute to the pathogenesis of AMD.
Kalayoglu
Murat V
MV
Angiogenesis Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA 02114, USA.
Bula
Deisy
D
Arroyo
Jorge
J
Gragoudas
Evangelos S
ES
D'Amico
Donald
D
Miller
Joan W
JW
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D002648:Child; D023521:Chlamydophila Infections / Q000382:microbiology*; D016993:Chlamydophila pneumoniae / Q000302:isolation & purification* / Q000502:physiology; D020256:Choroidal Neovascularization / Q000209:etiology / Q000382:microbiology*; D004269:DNA, Bacterial / Q000032:analysis; D015818:Eye Infections, Bacterial / Q000382:microbiology*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D016209:Interleukin-8 / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism / Q000382:microbiology; D008268:Macular Degeneration / Q000150:complications / Q000382:microbiology*; D008297:Male; D008875:Middle Aged; D010857:Pigment Epithelium of Eye / Q000378:metabolism / Q000382:microbiology; D016133:Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
C111835:CCL2 protein, human; D018932:Chemokine CCL2; D004269:DNA, Bacterial; D016209:Interleukin-8; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A