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M.V. Kalayoglu, D. Bula, J. Arroyo, E.S. Gragoudas, D. D'Amico, J.W. Miller; Chlamydia pneumoniae is identified in human choroidal neovascular membranes secondary to age–related macular degeneration and induces vascular endothelial growth factor in vitro . Invest. Ophthalmol. Vis. Sci. 2004;45(13):3128.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Age–related Macular Degeneration (AMD) and coronary artery disease share several risk factors, and these diseases may have similar pathogenic mechanisms that involve inflammation. The prokaryotic pathogen Chlamydia pneumoniae is an emerging risk factor in cardiovascular diseases, and recent seroepidemiological data have suggested that this pathogen also may be associated with AMD. In this study, we examined choroidal neovascular tissue (CNV) from patients with neovascular AMD for the presence of C. pneumoniae. In addition, we determined whether the pathogen dysregulates the function of key cell types in ways that can lead to CNV formation. Methods: Nine CNV removed from nine patients with neovascular AMD (ages 76–90) and five CNV removed from five patients without AMD were formalin–fixed and paraffin–embedded. In addition, nine frozen whole eyes from patients without AMD (ages 70–85) were obtained from the New England Eye Bank; these eyes were thawed, and retina, choroid and iris were individually isolated by dissection. DNA was extracted from some CNV and amplified with C. pneumoniae–specific primers (CP1–CP2 / CPC–CPD) using a touchdown–nested PCR technique. Furthermore, immunohistochemistry was performed on the CNV using a monoclonal antibody to C. pneumoniae (RR–402). Finally, human monocyte–derived macrophages and retinal pigment epithelial cells were exposed to C. pneumoniae and assayed for the production of pro–angiogenic immunomodulators (VEGF, IL–8, and MCP–1). Results: C. pneumoniae was present in 5 of 9 (56%) of CNV specimens by either PCR (2 of 9 specimens) or immunohistochemistry (4 of 9 specimens). One specimen was positive by both techniques. In contrast, C. pneumoniae was not detected from five non–AMD CNV by immunohistochemistry and nine normal eye–bank eyes by PCR. Positive PCR samples were subjected to automated sequencing and found to have 100% identity to the expected C. pneumoniae gene sequence. In addition, C. pneumoniae established productive infection in human macrophages and RPE cells; ELISA to key pro–angiogenic immunomodulators showed that C. pneumoniae infection dramatically induced VEGF by macrophages, and IL–8 and MCP–1 by RPE cells. Conclusions: These data indicate that a pathogen capable of inducing chronic inflammation and pro–angiogenic immunomodulators can be identified within human CNV secondary to AMD, and suggest that infection contributes to the pathogenesis of AMD.
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