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N. Matsumura, M. Tsujikawa, P. Xie, K. Nakai, Y. Saishin, M. Suzuki, H. Sakaguchi, M. Kamei; Lipopolysaccharide Pretreatment Suppresses Choroidal Neovascularization. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3360.
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© ARVO (1962-2015); The Authors (2016-present)
Humans are constantly exposed to low levels of lipopolysaccharide (LPS) through infection. Recent studies demonstrate that infections, like Chlamydia pneumonia, may be a risk factor for age-related macular degeneration. The purpose of this study is to evaluate whether LPS can modulate the development of choroidal neovascularization (CNV).
CNV was induced by laser photocoagulation in 8- to 10-week-old male C57BL/6 mice. Mice were given an intraperitoneal injection of 20µg LPS at 1, 2, 3 and 4 days before the laser treatment. As a control, PBS was administrated intraperitoneally. Serum levels of IL-10 were measured by ELISA over time. At 10 days after photocoagulation, mice were perfused with fluorescein-labeled dextran and euthanized. RPE-choroid-sclera flat mounts were prepared and the area of CNV was quantified with digital analysis software. As a second experiment, we intravitreally injected an anti-IL-10 antibody immediately after laser treatment in the mice with LPS pretreatment, and evaluated the CNV area.
The areas of CNV in the mice with LPS pretreatment at 1, 2, 3 and 4 days before photocoagulation were 16241, 14781, 15876, and 16606 µm2, respectively, which were significantly smaller than that of the control mice (21350µm2; p=0.047, 0.006, 0.028 and 0.057, respectively). The LPS CNV inhibitory effect was largest in the mice given LPS pretreatment 2 days before photocoagulation. After LPS pretreatment, serum IL-10 concentration increased (before, 1 and 2 days after treatment; 9.8, 207.8 and 92.8 pg/ml, respectively). Intravitreal injection of anti-IL-10 antibody inhibits CNV suppression by LPS pretreatment (p=0.0014).
CNV formation was suppressed by LPS pretreatment, presumably via IL-10 secretion. Our data suggested that increased IL-10 might be responsible for the CNV reduction. Low levels of LPS through infection can suppress the development of CNV.
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