Yuan Qu, Yujuan Liu, Junwei Fang, Chong Chen, Lu Cheng, Xiaoyin Xu, Jing Jin, Xia Chen, Tian Niu, Hanying Wang, Xindan Xing, Xin Shi, Yinchen Shen, Kun Liu
{"title":"UPLC-MS /MS脂质组学揭示的新生血管性年龄相关性黄斑变性患者血清脂质谱失调","authors":"Yuan Qu, Yujuan Liu, Junwei Fang, Chong Chen, Lu Cheng, Xiaoyin Xu, Jing Jin, Xia Chen, Tian Niu, Hanying Wang, Xindan Xing, Xin Shi, Yinchen Shen, Kun Liu","doi":"10.1186/s12944-025-02735-y","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>Neovascular age-related macular degeneration (nAMD) is a major aetiology of vision loss characterized by lipid metabolism dysregulation. This study investigated the alterations in lipid profiles associated with wet AMD (wAMD) and its subtype, polypoidal choroidal vasculopathy (PCV).</p><p><strong>Methods: </strong>A cross-sectional lipidomic analysis was derived from a prospective longitudinal study in China (2017-2019). Serum samples from 195 wAMD patients, 130 PCV patients and 119 controls were analysed using ultra-performance liquid chromatography‒tandem mass spectrometry (UPLC‒MS/MS), focusing on acylcarnitines, glycerophospholipids and sphingolipids. Training and test sets were randomly generated after sample size matching. Orthogonal partial least squares-discriminant (OPLS-DA), univariate and multivariate analyses were performed. The selection criteria for differential lipids were a variable importance in projection (VIP) > 1.0, a fold change (FC) > 1.2 or < 0.83, and a false discovery rate (FDR) < 0.05. Key lipids were refined using the Boruta algorithm and evaluated through Firth regression and receiver operating characteristic (ROC) analysis. Spearman's rank correlation analysis was used to assess the relationships between the differential lipids and ocular indicators, including central retinal thickness (CRT), central retinal volume (CRV) and best-corrected visual acuity (BCVA).</p><p><strong>Results: </strong>No significant Lipid profile differences were detected between wAMD and PCV. Compared with the controls, wAMD patients had 53 differential lipids (52 upregulated, 1 downregulated), whereas PCV patients had 34 (31 upregulated, 3 downregulated). Upregulated PC ae C42:0 was consistently associated with ocular indicators in both groups. A 9-lipid panel for wAMD and a 6-lipid panel for PCV showed moderate diagnostic performance in the ROC models. Significant correlations with macular structure and BCVA were observed in PCV patients for 12 phosphatidylcholines, 3 sphingomyelins and 2 acylcarnitines and in wAMD patients for one phosphatidylcholine and one acylcarnitine. Downregulated lipids were negatively correlated with CRT or CRV, whereas upregulated lipids showed the opposite trend. Age-related lipid associations were found in wAMD but not in PCV patients.</p><p><strong>Conclusions: </strong>PCV and wAMD had shared and distinct lipidomic dysregulations, with stronger systemic-retinal associations in PCV, suggesting that subtype-specific metabolic reprogramming may affect nAMD pathology, offering new perspectives regarding early diagnosis and intervention strategies to mitigate disease burden.</p><p><strong>Trial registration: </strong>NCT03128463 ( www.</p><p><strong>Clinicaltrial: </strong>gov ) was registered on 9 March 2017.</p>","PeriodicalId":18073,"journal":{"name":"Lipids in Health and Disease","volume":"24 1","pages":"302"},"PeriodicalIF":3.9000,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12481816/pdf/","citationCount":"0","resultStr":"{\"title\":\"Dysregulated serum lipid profiles in neovascular age-related macular degeneration revealed by UPLC‒MS/MS lipidomics.\",\"authors\":\"Yuan Qu, Yujuan Liu, Junwei Fang, Chong Chen, Lu Cheng, Xiaoyin Xu, Jing Jin, Xia Chen, Tian Niu, Hanying Wang, Xindan Xing, Xin Shi, Yinchen Shen, Kun Liu\",\"doi\":\"10.1186/s12944-025-02735-y\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>Neovascular age-related macular degeneration (nAMD) is a major aetiology of vision loss characterized by lipid metabolism dysregulation. This study investigated the alterations in lipid profiles associated with wet AMD (wAMD) and its subtype, polypoidal choroidal vasculopathy (PCV).</p><p><strong>Methods: </strong>A cross-sectional lipidomic analysis was derived from a prospective longitudinal study in China (2017-2019). Serum samples from 195 wAMD patients, 130 PCV patients and 119 controls were analysed using ultra-performance liquid chromatography‒tandem mass spectrometry (UPLC‒MS/MS), focusing on acylcarnitines, glycerophospholipids and sphingolipids. Training and test sets were randomly generated after sample size matching. Orthogonal partial least squares-discriminant (OPLS-DA), univariate and multivariate analyses were performed. The selection criteria for differential lipids were a variable importance in projection (VIP) > 1.0, a fold change (FC) > 1.2 or < 0.83, and a false discovery rate (FDR) < 0.05. Key lipids were refined using the Boruta algorithm and evaluated through Firth regression and receiver operating characteristic (ROC) analysis. Spearman's rank correlation analysis was used to assess the relationships between the differential lipids and ocular indicators, including central retinal thickness (CRT), central retinal volume (CRV) and best-corrected visual acuity (BCVA).</p><p><strong>Results: </strong>No significant Lipid profile differences were detected between wAMD and PCV. Compared with the controls, wAMD patients had 53 differential lipids (52 upregulated, 1 downregulated), whereas PCV patients had 34 (31 upregulated, 3 downregulated). Upregulated PC ae C42:0 was consistently associated with ocular indicators in both groups. A 9-lipid panel for wAMD and a 6-lipid panel for PCV showed moderate diagnostic performance in the ROC models. Significant correlations with macular structure and BCVA were observed in PCV patients for 12 phosphatidylcholines, 3 sphingomyelins and 2 acylcarnitines and in wAMD patients for one phosphatidylcholine and one acylcarnitine. Downregulated lipids were negatively correlated with CRT or CRV, whereas upregulated lipids showed the opposite trend. 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Dysregulated serum lipid profiles in neovascular age-related macular degeneration revealed by UPLC‒MS/MS lipidomics.
Purpose: Neovascular age-related macular degeneration (nAMD) is a major aetiology of vision loss characterized by lipid metabolism dysregulation. This study investigated the alterations in lipid profiles associated with wet AMD (wAMD) and its subtype, polypoidal choroidal vasculopathy (PCV).
Methods: A cross-sectional lipidomic analysis was derived from a prospective longitudinal study in China (2017-2019). Serum samples from 195 wAMD patients, 130 PCV patients and 119 controls were analysed using ultra-performance liquid chromatography‒tandem mass spectrometry (UPLC‒MS/MS), focusing on acylcarnitines, glycerophospholipids and sphingolipids. Training and test sets were randomly generated after sample size matching. Orthogonal partial least squares-discriminant (OPLS-DA), univariate and multivariate analyses were performed. The selection criteria for differential lipids were a variable importance in projection (VIP) > 1.0, a fold change (FC) > 1.2 or < 0.83, and a false discovery rate (FDR) < 0.05. Key lipids were refined using the Boruta algorithm and evaluated through Firth regression and receiver operating characteristic (ROC) analysis. Spearman's rank correlation analysis was used to assess the relationships between the differential lipids and ocular indicators, including central retinal thickness (CRT), central retinal volume (CRV) and best-corrected visual acuity (BCVA).
Results: No significant Lipid profile differences were detected between wAMD and PCV. Compared with the controls, wAMD patients had 53 differential lipids (52 upregulated, 1 downregulated), whereas PCV patients had 34 (31 upregulated, 3 downregulated). Upregulated PC ae C42:0 was consistently associated with ocular indicators in both groups. A 9-lipid panel for wAMD and a 6-lipid panel for PCV showed moderate diagnostic performance in the ROC models. Significant correlations with macular structure and BCVA were observed in PCV patients for 12 phosphatidylcholines, 3 sphingomyelins and 2 acylcarnitines and in wAMD patients for one phosphatidylcholine and one acylcarnitine. Downregulated lipids were negatively correlated with CRT or CRV, whereas upregulated lipids showed the opposite trend. Age-related lipid associations were found in wAMD but not in PCV patients.
Conclusions: PCV and wAMD had shared and distinct lipidomic dysregulations, with stronger systemic-retinal associations in PCV, suggesting that subtype-specific metabolic reprogramming may affect nAMD pathology, offering new perspectives regarding early diagnosis and intervention strategies to mitigate disease burden.
Trial registration: NCT03128463 ( www.
Clinicaltrial: gov ) was registered on 9 March 2017.
期刊介绍：
Lipids in Health and Disease is an open access, peer-reviewed, journal that publishes articles on all aspects of lipids: their biochemistry, pharmacology, toxicology, role in health and disease, and the synthesis of new lipid compounds.
Lipids in Health and Disease is aimed at all scientists, health professionals and physicians interested in the area of lipids. Lipids are defined here in their broadest sense, to include: cholesterol, essential fatty acids, saturated fatty acids, phospholipids, inositol lipids, second messenger lipids, enzymes and synthetic machinery that is involved in the metabolism of various lipids in the cells and tissues, and also various aspects of lipid transport, etc. In addition, the journal also publishes research that investigates and defines the role of lipids in various physiological processes, pathology and disease. In particular, the journal aims to bridge the gap between the bench and the clinic by publishing articles that are particularly relevant to human diseases and the role of lipids in the management of various diseases.
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