Choroidal neovascularization enhanced by chlamydia pneumoniae via toll-like receptor 2 in the retinal pigment epithelium

Takeshi Fujimoto, Koh Hei Sonoda, Kuniaki Hijioka, Kohta Sato, Atsunobu Takeda, Eiichi Hasegawa, Yuji Oshima, Tatsuro Ishibashi

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Abstract

PURPOSE. Choroidal neovascularization (CNV) is directly related to visual loss in persons with age-related macular degeneration (AMD) and other macular disorders. Chlamydia pneumoniae, a prokaryotic pathogen that causes chronic inflammation, is recognized as a risk factor for cardiovascular diseases. In this study, the authors investigated the association between C. pneumoniae infection and AMD using a laser-induced CNV model in mice. METHODS. C57BL/6 mice, myeloid differentiation factor (MyD) 88 knockout (KO) mice, Toll-like receptor (TLR) 2 KO mice, and TLR4 KO mice were used. Experimental CNV was induced by rupturing the Bruch's membrane by laser photocoagulation (PC). Seven days after PC, the eyes were enucleated and the areas of CNV were measured in choroidal flat mounts. Cytokine gene expression by quantitative real-time PCR in the primary cultured retinal pigment epithelium (RPE) cells was also examined. RESULTS. Vitreous injection of the C. pneumoniae antigen increased the size of CNV. Although lipopolysaccharide stimulation can induce multiple cytokines, cultured mouse RPE cells from C57BL/6 mice expressed IL-6 and VEGF, but not TNF-α mRNA, in response to C. pneumoniae antigen. RPE cells from either MyD88 KO mice or TLR2 KO mice did not respond to the C. pneumoniae antigen. TLR2 KO mice did not augment the size increase of experimental CNV by C. pneumoniae antigen in vivo. CONCLUSIONS. C. pneumoniae can trigger inflammatory responses in the eye and promote experimental CNV in a TLR2- dependent manner. These data provide experimental evidence to imply persistent C. pneumoniae infection is a risk factor for AMD.

Original languageEnglish
Pages (from-to)4694-4702
Number of pages9
JournalInvestigative Ophthalmology and Visual Science
Volume51
Issue number9
DOIs
Publication statusPublished - Sep 1 2010

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All Science Journal Classification (ASJC) codes

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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