Systemic Lipopolysaccharide Exposure Exacerbates Choroidal Neovascularization in Mice

This study aims to investigate the effect of a systemic lipopolysaccharide (LPS) stimulus in the course of laser-induced choroidal neovascularization (CNV) in C57BL/6 J mice. A group of CNV-subjected mice received 1 mg/kg LPS via the tail vein immediately after CNV induction. Mouse eyes were monitored <i>in vivo</i> with fluorescein angiography for 2 weeks. <i>In situ</i> hybridization and flow cytometry were performed in the retina at different time points. LPS led to increased fluorescein leakage 3 days after CNV, correlated with a large influx of monocyte-derived macrophages and increase of pro-inflammatory microglia/macrophages in the retina. Additionally, LPS enhanced <i>Vegfα</i> mRNA expression by <i>Glul</i>-expressing cells but not <i>Aif1</i> positive microglia/macrophages in the laser lesion. These findings suggest that systemic LPS exposure has transient detrimental effects in the course of CNV through activation of microglia/macrophages to a pro-inflammatory phenotype and supports the important role of these cells in the CNV course.

本研究旨在探讨系统性脂多糖（lipopolysaccharide, LPS）刺激对C57BL/6J小鼠激光诱导脉络膜新生血管（choroidal neovascularization, CNV）病程的影响。一组接受CNV造模的小鼠于CNV诱导完成后即刻经尾静脉注射1 mg/kg LPS。采用荧光素血管造影（fluorescein angiography）对小鼠眼部进行为期2周的体内（in vivo）监测。在不同时间点对视网膜开展原位杂交（in situ hybridization）与流式细胞术（flow cytometry）检测。CNV造模3天后，LPS处理可导致荧光素渗漏加剧，该现象与视网膜内单核细胞源性巨噬细胞大量浸润以及促炎型小胶质细胞/巨噬细胞比例升高显著相关。此外，LPS可通过表达Glul的细胞上调Vegfα mRNA的表达，但未影响激光损伤灶内Aif1阳性的小胶质细胞/巨噬细胞。上述研究结果表明，系统性LPS暴露可通过将小胶质细胞/巨噬细胞极化为促炎表型，对CNV病程产生一过性有害影响，并证实了这类细胞在CNV病程中的重要作用。