Preliminary insights into serum metabolomics in atrophic myopic maculopathy: potential link to fatty acid metabolism dysregulation

Abstract Introduction: Atrophic myopic maculopathy (AMM) causes irreversible and progressive visual impairment. Metabolomics offers a valuable opportunity for exploring the pathological mechanisms of AMM and identifying potential therapeutic targets. This study compared serum metabolite profiles bet...

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Main Authors: Yuanyuan Fan, Bintao Xie, Lifeng Chen, Mengai Wu, Li Lin, Zhijie Wang, Bin Zheng
Format: Article
Language:English
Published: BMC 2025-07-01
Series:BMC Ophthalmology
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Online Access:https://doi.org/10.1186/s12886-025-04220-7
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author Yuanyuan Fan
Bintao Xie
Lifeng Chen
Mengai Wu
Li Lin
Zhijie Wang
Bin Zheng
author_facet Yuanyuan Fan
Bintao Xie
Lifeng Chen
Mengai Wu
Li Lin
Zhijie Wang
Bin Zheng
author_sort Yuanyuan Fan
collection DOAJ
description Abstract Introduction: Atrophic myopic maculopathy (AMM) causes irreversible and progressive visual impairment. Metabolomics offers a valuable opportunity for exploring the pathological mechanisms of AMM and identifying potential therapeutic targets. This study compared serum metabolite profiles between patients with high myopia with and without AMM. Methods: This case–control study included 57 adults with high myopia (30 with AMM, 27 without AMM). Clinical data including body mass index (BMI), fasting blood glucose, and lipid profiles were recorded. Serum samples were analyzed using untargeted metabolomics based on ultra-high-performance liquid chromatography–tandem mass spectrometry (UHPLC–MS/MS). Differential metabolites were first screened for their discriminative performance using receiver operating characteristic (ROC) curves. Weighted gene co-expression network analysis (WGCNA) was then applied to explore co-expression patterns and identify metabolite modules associated with clinical traits. Multivariate logistic regression was performed to identify independent metabolic predictors of AMM. Results: Compared with controls, patients with AMM showed significant alterations in serum metabolites, including 18 upregulated and 26 downregulated compounds, enriched in 5 pathways. WGCNA and ROC analysis identified 11 potential biomarkers associated with atrophy grades in AMM. Three metabolites were independently associated with AMM after adjustment: triglyceride (OR = 2.73, p = 0.021), ln[Tetracosahexaenoic acid] (OR = 3.54, p = 0.004), and ln[Decanoylcarnitine] (OR = 0.37, p = 0.025). The model showed good fit (χ² = 22.89, p < 0.001) with 71.9% accuracy and AUC = 0.821 (95% CI: 0.715–0.927). Conclusions: This study provides exploratory evidence of dysregulated serum fatty acid metabolism in AMM. These findings suggest that such metabolic alterations may be associated with mitochondrial dysfunction and inflammatory processes, offering a potential direction for future mechanistic and therapeutic research.
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spelling doaj-art-da458a2c66ba4702b6c46013f6b1c2ee2025-08-20T03:03:34ZengBMCBMC Ophthalmology1471-24152025-07-0125111310.1186/s12886-025-04220-7Preliminary insights into serum metabolomics in atrophic myopic maculopathy: potential link to fatty acid metabolism dysregulationYuanyuan Fan0Bintao Xie1Lifeng Chen2Mengai Wu3Li Lin4Zhijie Wang5Bin Zheng6NationalClinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical UniversityState Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical UniversityNationalClinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical UniversityNationalClinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical UniversityNationalClinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical UniversityNationalClinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical UniversityNationalClinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical UniversityAbstract Introduction: Atrophic myopic maculopathy (AMM) causes irreversible and progressive visual impairment. Metabolomics offers a valuable opportunity for exploring the pathological mechanisms of AMM and identifying potential therapeutic targets. This study compared serum metabolite profiles between patients with high myopia with and without AMM. Methods: This case–control study included 57 adults with high myopia (30 with AMM, 27 without AMM). Clinical data including body mass index (BMI), fasting blood glucose, and lipid profiles were recorded. Serum samples were analyzed using untargeted metabolomics based on ultra-high-performance liquid chromatography–tandem mass spectrometry (UHPLC–MS/MS). Differential metabolites were first screened for their discriminative performance using receiver operating characteristic (ROC) curves. Weighted gene co-expression network analysis (WGCNA) was then applied to explore co-expression patterns and identify metabolite modules associated with clinical traits. Multivariate logistic regression was performed to identify independent metabolic predictors of AMM. Results: Compared with controls, patients with AMM showed significant alterations in serum metabolites, including 18 upregulated and 26 downregulated compounds, enriched in 5 pathways. WGCNA and ROC analysis identified 11 potential biomarkers associated with atrophy grades in AMM. Three metabolites were independently associated with AMM after adjustment: triglyceride (OR = 2.73, p = 0.021), ln[Tetracosahexaenoic acid] (OR = 3.54, p = 0.004), and ln[Decanoylcarnitine] (OR = 0.37, p = 0.025). The model showed good fit (χ² = 22.89, p < 0.001) with 71.9% accuracy and AUC = 0.821 (95% CI: 0.715–0.927). Conclusions: This study provides exploratory evidence of dysregulated serum fatty acid metabolism in AMM. These findings suggest that such metabolic alterations may be associated with mitochondrial dysfunction and inflammatory processes, offering a potential direction for future mechanistic and therapeutic research.https://doi.org/10.1186/s12886-025-04220-7Atrophic myopic maculopathyUntargeted metabolomicsFatty acid metabolismMitochondrial dysfunctionInflammation
spellingShingle Yuanyuan Fan
Bintao Xie
Lifeng Chen
Mengai Wu
Li Lin
Zhijie Wang
Bin Zheng
Preliminary insights into serum metabolomics in atrophic myopic maculopathy: potential link to fatty acid metabolism dysregulation
BMC Ophthalmology
Atrophic myopic maculopathy
Untargeted metabolomics
Fatty acid metabolism
Mitochondrial dysfunction
Inflammation
title Preliminary insights into serum metabolomics in atrophic myopic maculopathy: potential link to fatty acid metabolism dysregulation
title_full Preliminary insights into serum metabolomics in atrophic myopic maculopathy: potential link to fatty acid metabolism dysregulation
title_fullStr Preliminary insights into serum metabolomics in atrophic myopic maculopathy: potential link to fatty acid metabolism dysregulation
title_full_unstemmed Preliminary insights into serum metabolomics in atrophic myopic maculopathy: potential link to fatty acid metabolism dysregulation
title_short Preliminary insights into serum metabolomics in atrophic myopic maculopathy: potential link to fatty acid metabolism dysregulation
title_sort preliminary insights into serum metabolomics in atrophic myopic maculopathy potential link to fatty acid metabolism dysregulation
topic Atrophic myopic maculopathy
Untargeted metabolomics
Fatty acid metabolism
Mitochondrial dysfunction
Inflammation
url https://doi.org/10.1186/s12886-025-04220-7
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