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Induction of Ocular Surface Inflammation and Collection of Involved Tissues
Published on: August 4, 2022
Low-dose lipopolysaccharide pretreatment suppresses choroidal neovascularization via IL-10 induction
Nagakazu Matsumura1, Motohiro Kamei, Motokazu Tsujikawa
1Department of Ophthalmology, Osaka University Graduate School of Medicine, Osaka, Japan.
Abstract:
Recent studies have suggested that some kinds of microbial infection may have a crucial role in the development of many diseases such as autoimmune diseases and certain types of cancer. It has been reported that some chronic infections, such as Chlamydia pneumoniae, and immunological dysfunctions are associated with age-related macular degeneration (AMD), a leading cause of blindness. To evaluate the association between systemic low-level inflammation induced by infection and AMD pathogenesis, we investigated whether intraperitoneal injection of lipopolysaccharide (LPS) can modulate the development of laser-induced choroidal neovascularization (CNV), a key feature of AMD. Contrary to our expectations, the sizes of CNV in mice with LPS pretreatment were approximately 65% smaller than those of the control mice. After LPS pretreatment, serum IL-10 concentration and IL-10 gene expression in peritoneal macrophages and in the posterior part of the eye increased. Peritoneal injection of anti-IL10 antibody reduced CNV suppression by LPS pretreatment. Moreover, adoptive transfer of the resident peritoneal macrophages from LPS-treated mice into control littermates resulted in an approximately 26% reduction in the size of CNV compared with PBS-treated mice. We concluded that CNV formation was suppressed by low-dose LPS pretreatment via IL-10 production by macrophages.
Insights
Low-dose lipopolysaccharide (LPS) pretreatment suppressed age-related macular degeneration (AMD) progression in mice. This protective effect was mediated by increased interleukin-10 (IL-10) production from macrophages, highlighting a novel therapeutic pathway for AMD.
Area of Science:
- Ophthalmology
- Immunology
- Microbiology
Background:
- Microbial infections are increasingly linked to diseases like cancer and autoimmune conditions.
- Chronic infections and immune dysfunction are associated with age-related macular degeneration (AMD).
Purpose of the Study:
- To investigate the role of systemic low-level inflammation in AMD pathogenesis.
- To determine if lipopolysaccharide (LPS) pretreatment modulates the development of laser-induced choroidal neovascularization (CNV), a key feature of AMD.
Main Methods:
- Mice underwent intraperitoneal injection of LPS before laser-induced CNV.
- Measurements of CNV size, serum IL-10 levels, and IL-10 gene expression were performed.
- Experiments involved anti-IL-10 antibody administration and adoptive transfer of peritoneal macrophages.
Main Results:
- LPS pretreatment significantly reduced CNV size by approximately 65%.
- IL-10 concentration and gene expression increased in serum, peritoneal macrophages, and ocular tissues post-LPS.
- Anti-IL-10 antibody blocked the suppressive effect of LPS, and macrophage transfer reduced CNV size by 26%.
Conclusions:
- Low-dose LPS pretreatment suppresses CNV formation via IL-10 production by macrophages.
- This suggests a potential therapeutic strategy for AMD involving modulation of the immune response to microbial components.