Dataset Information

Metabolomic analysis of aqueous humor reveals potential metabolite biomarkers for differential detection of macular edema.

ABSTRACT:

Background

Macular edema (ME) is a major complication of retinal disease with multiple mechanisms involved in its development. This study aimed to investigate the metabolite profile of aqueous humor (AH) in patients with ME of different etiologies and identify potential metabolite biomarkers for early diagnosis of ME.

Methods

Samples of AH were collected from 60 patients with ME and 20 age- and sex-matched controls and analyzed by liquid chromatography-mass spectrometry (LC/MS)-based metabolomics. A series of univariate and multivariate statistical analyses were performed to identify differential metabolites and enriched metabolite pathways.

Results

The metabolic profile of AH differed significantly between ME patients and healthy controls, and differentially expressed metabolites were identified. Pathway analysis revealed that these differentially expressed metabolites are mainly involved in lipid metabolism and amino acid metabolism. Moreover, significant differences were identified in the metabolic composition of AH from patients with ME due to different retinal diseases including age-related macular degeneration (AMD-ME), diabetic retinopathy (DME) and branch retinal vein occlusion (BRVO-ME). In total, 39 and 79 etiology-specific altered metabolites were identified for AMD-ME and DME, respectively. Finally, an AH-derived machine learning-based diagnostic model was developed and successfully validated in the test cohort with an area under the receiver operating characteristic (ROC) curve of 0.79 for AMD-ME, 0.94 for DME and 0.77 for BRVO-ME.

Conclusions

Our study illustrates the potential underlying metabolic basis of AH of different etiologies across ME populations. We also identify AH-derived metabolite biomarkers that may improve the differential diagnosis and treatment stratification of ME patients with different etiologies.

SUBMITTER: Jiang D

PROVIDER: S-EPMC10067239 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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Publications

Metabolomic analysis of aqueous humor reveals potential metabolite biomarkers for differential detection of macular edema.

Jiang Dan D Yan Congcong C Ge Lina L Yang Chun C Huang Ying Y Chan Yau Kei YK Chen Chonghua C Chen Wei W Zhou Meng M Lin Bing B

Eye and vision (London, England) 20230401 1

<h4>Background</h4>Macular edema (ME) is a major complication of retinal disease with multiple mechanisms involved in its development. This study aimed to investigate the metabolite profile of aqueous humor (AH) in patients with ME of different etiologies and identify potential metabolite biomarkers for early diagnosis of ME.<h4>Methods</h4>Samples of AH were collected from 60 patients with ME and 20 age- and sex-matched controls and analyzed by liquid chromatography-mass spectrometry (LC/MS)-ba ...[more]

PMID: 37004107

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Project description:Macular edema (ME) is the main cause of visual impairment in patients with retinal vein occlusion (RVO). The degree of ME affects the prognosis of RVO patients, while it lacks objective laboratory biomarkers. We aimed to compare aqueous humor samples from 28 patients with retinal vein occlusion macular edema (RVO-ME) to 27 age- and sex-matched controls by ultra-high-performance liquid chromatography equipped with quadrupole time-of-flight mass spectrometry, so as to identify the key biomarkers and to increase the understanding of the mechanism of RVO-ME at the molecular level. Through univariate and multivariate statistical analyses, we identified 60 metabolites between RVO-ME patients and controls and 40 differential metabolites in mild RVO-ME [300 μm ≤ central retinal thickness (CRT) < 400 μm] patients compared with severe RVO-ME (CRT ≥ 400 μm). Pathway enrichment analysis showed that valine, leucine, and isoleucine biosynthesis; ascorbate and aldarate metabolism; and pantothenate and coenzyme A biosynthesis were significantly altered in RVO-ME in comparison with controls. Compared with mild RVO-ME, degradation and biosynthesis of valine, leucine, and isoleucine; histidine metabolism; beta-alanine metabolism; and pantothenate and coenzyme A biosynthesis were significantly changed in severe RVO-ME. Furthermore, the receiver operating characteristic (ROC) curve analysis revealed that adenosine, threonic acid, pyruvic acid, and pyro-L-glutaminyl-l-glutamine could differentiate RVO-ME from controls with an area under the curve (AUC) of >0.813. Urocanic acid, diethanolamine, 8-butanoylneosolaniol, niacinamide, paraldehyde, phytosphingosine, 4-aminobutyraldehyde, dihydrolipoate, and 1-(beta-D-ribofuranosyl)-1,4-dihydronicotinamide had an AUC of >0.848 for distinguishing mild RVO-ME from severe RVO-ME. Our study expanded the understanding of metabolomic changes in RVO-ME, which could help us to have a good understanding of the pathogenesis of RVO-ME.

Project description:Importance:Variability in response to anti-vascular endothelial growth factor (VEGF) treatment in diabetic macular edema (DME) remains a significant clinical challenge. Biomarkers could help anticipate responses to anti-VEGF therapy. Objectives:To investigate aqueous humor cytokine level changes in response to intravitreal ranibizumab therapy for the management of DME, and to determine the association between baseline aqueous levels and anatomic response. Design, Setting, and Participants:In this prospective multicenter cohort study, 49 participants with diabetes mellitus complicated by center-involving DME, with a central subfield thickness of 310 μm or greater on spectral-domain optical coherence tomography (SD-OCT), were recruited from December 22, 2011, to June 13, 2013 and statistical analysis were performed from March 1, 2017, to June 1, 2017. A total of 48 participants proceeded to follow-up. Interventions:Participants received monthly injections of ranibizumab, 0.5 mg, for 3 months. Aqueous fluid for cytokine analysis was obtained at baseline and repeated at the 2-month visit. Multiplex immunoassay was carried out in duplicate for VEGF, placental growth factor, transforming growth factor beta 2, intercellular adhesion molecule 1 (ICAM-1), interleukin 6 (IL-6), IL-8, IL-10, vascular intercellular adhesion molecule, and monocyte chemoattractant protein 1. Main Outcomes and Measures:Baseline and 2-month change in aqueous cytokine levels, 3-month change in SD-OCT central subfield thickness and macular volume (MV), and the statistical association between baseline aqueous cytokine levels and these measures of anatomic response to ranibizumab in center-involving DME. Results:Among the 48 participants, the mean (SD) age was 61.9 (7.1) years and 36 participants (75.0%) were men. The following cytokines were lower at month 2 vs baseline: ICAM-1 (median change, -190.88; interquartile range [IQR], -634.20 to -26.54; P < .001), VEGF (median change, -639.45; IQR, -1040.61 to -502.61; P < .001), placental growth factor (median change, -1.31; IQR, -5.99 to -0.01; P < .001), IL-6 (median change, -38.61; IQR, -166.72 to -2.80; P < .001), and monocyte chemoattractant protein 1 (median change, -90.13; IQR, -382.74 to 109.47; P = .01). When controlling for age, foveal avascular zone size, and severity of retinopathy, multiple linear regression determined that increasing baseline aqueous ICAM-1 was associated with a favorable anatomic response, in terms of reduced SD-OCT MV at 3 months (every additional 100 pg/mL of baseline ICAM-1 was associated with a reduction of 0.0379 mm3; P = .01). Conversely, increasing baseline aqueous VEGF was associated with a less favorable SD-OCT MV response at 3 months (every additional 100 pg/mL of baseline VEGF was associated with an increase of 0.0731 mm3; P = .02) and was associated with lower odds of being a central subfield thickness responder (odds ratio, 0.868; 95% CI, 0.755-0.998). Conclusions and Relevance:Elevated aqueous ICAM-1 and reduced VEGF levels at baseline are associated with a favorable anatomic response to ranibizumab in DME, although there is not always direct correlation between anatomic and visual acuity response.

Project description:PurposeTo explore the alterations in metabolites of wet age-related macular degeneration (wAMD) by conducting metabolomics in aqueous humor from patients with wAMD and to assess the potential effects of anti-vascular endothelial growth factor (anti-VEGF) on these metabolites.MethodsMetabolomic analysis was performed on the aqueous humor of 30 patients with wAMD receiving anti-VEGF treatments and 20 controls, via ultra-high performance liquid chromatography tandem mass spectrometry. The aqueous humor samples collected from untreated patients with wAMD were classified as the pre-wAMD group. Accordingly, the samples collected from patients with wAMD receiving one anti-VEGF treatment were designated as the post-wAMD group. Individuals were further classified into responders and nonresponders according to their reaction to the treatment. Principal component analysis, hierarchical cluster analysis, and the Kyoto Encyclopedia of Genes and Genomes annotation and enrichment analysis, were subsequently performed. Machine learning and receiver operating characteristic curve analyses were used to further analyze potential vital metabolites.ResultsAmong the 1001 metabolites verified in the aqueous humor, 306 compounds separated patients with pre-wAMD from the control group, whereas 68 metabolites differentiated patients with post-wAMD and patients with pre-wAMD. Enrichment in metabolic pathways was noted in ABC transporters, thiamine metabolism, glycerophospholipid metabolism, mammalian target of rapamycin signaling pathway and tyrosine metabolism, and so on. Machine learning and receiver operating characteristic curves analysis suggested that δ-valerolactam could not only distinguish between patients with wAMD and the control group, but also differentiate between patients with post-wAMD and patients with pre-wAMD. Changes in acylcarnitine were observed in anti-VEGF responders with wAMD.ConclusionsThere were noticeable alterations in the aqueous humor of patients with wAMD involving many metabolites that are associated with ABC transporters, glycerophospholipid metabolism, and the mammalian target of rapamycin signaling pathway. It is possible that δ-valerolactam can be applied as a biomarker in wAMD.

Dataset Information

Metabolomic analysis of aqueous humor reveals potential metabolite biomarkers for differential detection of macular edema.

Background

Methods

Results

Conclusions

Publications

Metabolomic analysis of aqueous humor reveals potential metabolite biomarkers for differential detection of macular edema.

Similar Datasets

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