Systemic Lipopolysaccharide Exposure Exacerbates Choroidal Neovascularization in Mice

Abstract

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 in vivo with fluorescein angiography for 2 weeks. In situ 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 Vegfα mRNA expression by Glul-expressing cells but not Aif1 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.

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“…Increased LPS concentrations act as potent immune activators and toll-like receptor (TLR) 4 (TLR4) ligands, triggering inflammation ( Chassaing and Gewirtz, 2014 ; Scott et al, 2017 ). Within the eye, various cells, such as perivascular macrophages, microglia, photoreceptors, dendritic cells, and RPE cells, exhibit proinflammatory signals via LPS ( Tsioti et al, 2022 ). LPS-induced retinal explants exhibited a notable neuroinflammatory reaction, marked by deterioration of neurons and increased levels of various cytokines ( Ghosh et al, 2018 ).…”