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.

KEYWORDS:

• Choroidal neovascularization
• lipopolysaccharide
• microglia
• monocyte-derived macrophages
• retina
• systemic infection

Acknowledgments

The authors would like to thank the Department for BioMedical Research (DBMR) of the University of Bern for the facilities and scientific and technical assistance.

Disclosure statement

I.T., Boehringer Ingelheim (F); B.S., None; P.E., Novartis Pharma Schweiz (C); M.S.Z.,Bayer (F, C), Heidelberg Engineering (S), Novartis (C, I), Boehringer Ingelheim (F); P.M.B., Boehringer Ingelheim (E); D. K., Boehringer Ingelheim (F).

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/09273948.2022.2147547

Additional information

Funding

The study was supported by a grant from Boehringer Ingelheim.