Metabolomics Unveils the Role of Pipecolic Acid in Regulating Monocytes/Macrophages-Endothelial Cells Crosstalk to Modulate Choroidal Neovascularization.

Abstract

Choroidal neovascularization (CNV) is a leading cause of vision loss in ocular diseases, including age-related macular degeneration (AMD). Despite extensive research, the underlying mechanisms of CNV remain incompletely understood, with a predominant focus on endothelial dysfunction. CNV, however, is a multi-cellular, multi-stage process involving complex interactions between endothelial cells, monocytes/macrophages, and other immune cells. In this study, we employed a dual-platform metabolomics approach combining liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS) to identify key metabolic alterations associated with CNV. Our results revealed significant changes in metabolic pathways during CNV progression. Using a myeloid lineage tracing mouse model, we further explored how Pipecolic acid regulates interactions between monocytes/macrophages and endothelial cells, key players in CNV development. We found that Pipecolic acid modulates monocyte/macrophage-endothelial cell crosstalk, inhibiting pathological angiogenesis. These results provide valuable insights into the molecular mechanisms driving CNV and highlight potential therapeutic targets for treating ocular neovascular diseases.