Metabolomics unveils the role of pipecolic acid in regulating monocytes/macrophages-endothelial cells crosstalk to modulate choroidal neovascularization

IF 3 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research Pub Date : 2025-02-26 DOI:10.1016/j.exer.2025.110315

Chang Liu , Fangcheng Xu , Ruoyan Wei , Yun Cheng , Yunzhe Wang , Yefei Shi , Ke Yang , Wenhui Peng , Weixia Jian , Haixiang Wu , Meiyan Li

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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.

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代谢组学揭示了哌泊醇酸在调节单核细胞/巨噬细胞-内皮细胞串联以调节脉络膜新生血管中的作用。

脉络膜新生血管（CNV）是眼部疾病视力丧失的主要原因，包括年龄相关性黄斑变性（AMD）。尽管进行了广泛的研究，但CNV的潜在机制仍然不完全清楚，主要集中在内皮功能障碍上。然而，CNV是一个多细胞、多阶段的过程，涉及内皮细胞、单核/巨噬细胞和其他免疫细胞之间复杂的相互作用。在这项研究中，我们采用了双平台代谢组学方法，结合液相色谱-质谱（LC-MS）和气相色谱-质谱（GC-MS）来识别与CNV相关的关键代谢改变。我们的研究结果揭示了CNV进展过程中代谢途径的显著变化。使用骨髓谱系追踪小鼠模型，我们进一步探索了Pipecolic酸如何调节单核细胞/巨噬细胞和内皮细胞之间的相互作用，内皮细胞是CNV发展的关键参与者。我们发现，细果酸调节单核细胞/巨噬细胞-内皮细胞串扰，抑制病理性血管生成。这些结果为研究CNV的分子机制提供了有价值的见解，并突出了治疗眼部新生血管疾病的潜在治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Experimental eye research 医学-眼科学

CiteScore

6.80

自引率

5.90%

发文量

323

审稿时长

66 days

期刊介绍： The primary goal of Experimental Eye Research is to publish original research papers on all aspects of experimental biology of the eye and ocular tissues that seek to define the mechanisms of normal function and/or disease. Studies of ocular tissues that encompass the disciplines of cell biology, developmental biology, genetics, molecular biology, physiology, biochemistry, biophysics, immunology or microbiology are most welcomed. Manuscripts that are purely clinical or in a surgical area of ophthalmology are not appropriate for submission to Experimental Eye Research and if received will be returned without review.