Choroidal neovascularization enhanced by Chlamydia pneumoniae via Toll-like receptor 2 in the retinal pigment epithelium.
OBJECTIVE
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-alpha 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.
Fujimoto
Takeshi
T
Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Sonoda
Koh-Hei
KH
Hijioka
Kuniaki
K
Sato
Kohta
K
Takeda
Atsunobu
A
Hasegawa
Eiichi
E
Oshima
Yuji
Y
Ishibashi
Tatsuro
T
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D023521:Chlamydophila Infections / Q000150:complications* / Q000453:epidemiology / Q000276:immunology; D016993:Chlamydophila pneumoniae; D020256:Choroidal Neovascularization / Q000276:immunology / Q000382:microbiology*; D002908:Chronic Disease; D005260:Female; D005451:Fluorescein Angiography; D015850:Interleukin-6 / Q000378:metabolism; D008268:Macular Degeneration / Q000453:epidemiology / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000166:cytology / Q000276:immunology / Q000382:microbiology*; D012307:Risk Factors; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D000942:Antigens, Bacterial; D015850:Interleukin-6; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse