Untargeted metabolomics for uncovering plasma biological markers of wet age-related macular degeneration

Deng, Yao; Shuai, Ping; Wang, Haixin; Zhang, Shanshan; Li, Jie; Du, Mingyan; Huang, Peng; Qu, Chao; Huang, Lulin

doi:10.18632/aging.203006

Cited by 20 publications

(15 citation statements)

References 65 publications

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“…Several components of the lipid metabolome have been linked to PCV through epidemiologic, genetic and biochemical studies [ 92 – 94 ]. Metabolomic studies have implicated several oxidised lipids and amino acids, including hyodeoxycholic acid and L-tryptophanamide, as retinal epithelial modulators with differential abundance in PCV compared to typical nAMD [ 95 ]. Both species influenced apoptosis and necrosis in cultured RPE and retinal endothelial cells.…”

Section: Future Research Directionsmentioning

confidence: 99%

Evolving treatment paradigms for PCV

Fenner

Cheung

Sim

et al. 2021

Eye

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Polypoidal choroidal vasculopathy (PCV) is a subtype of neovascular AMD (nAMD) that accounts for a significant proportion of nAMD cases worldwide, and particularly in Asia. Contemporary PCV treatment strategies have closely followed those used in typical nAMD, though there are significant gaps in knowledge on PCV management and it remains unclear if these strategies are appropriate. Current clinical trial data suggest intravitreal anti-vascular endothelial growth factor (VEGF) therapy alone or in combination with photodynamic therapy is effective in managing haemorrhage and exudation in PCV, although the optimal treatment interval, including as-needed and treat-and-extend approaches, is unclear. Newer imaging modalities, including OCT angiography and high-resolution spectral domain OCT have enabled characterisation of unique PCV biomarkers that may provide guidance on how and when treatment and re-treatment should be initiated. Treatment burden for PCV is a major focus of future therapeutic research and several newly developed anti-VEGF agents, including brolucizumab, faricimab, and new modes of drug delivery like the port delivery system, offer hope for dramatically reduced treatment burden for PCV patients. Beyond anti-VEGF therapy, recent developments in our understanding of PCV pathophysiology, in particular the role of choroidal anatomy and lipid mediators in PCV pathogenesis, offer new treatment avenues that may become clinically relevant in the future. This article explores the current management of PCV and more recent approaches to PCV treatment based on an improved understanding of this unique disease process.

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Section: Future Research Directionsmentioning

confidence: 99%

Evolving treatment paradigms for PCV

Fenner

Cheung

Sim

et al. 2021

Eye

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“…Due to the small number of patients with late AMD, we also did not perform analysis comparing urinary profiles of exudative and dry AMD. This would be interesting as it is likely that these differ, and other authors have described different levels of phosphoethanolamines in patients with neovascular AMD and controls [30]. The external validity of our study might also be limited because our cohorts were nearly all Caucasian subjects.…”

Section: Discussionmentioning

confidence: 92%

“…Each model included a single metabolite as a continuous variable, adjusting for age, gender, BMI, and use of AREDS vitamins supplementation at the time of study inclusion. Initially, models were computed for the two study cohorts (Boston, US and Coimbra, Portugal) separately, and then these were meta-analyzed using a fixed-effects method [30]. For each model, in addition to the meta-analysis p-values, we provide the odds ratio of each metabolite for both cohorts.…”

Section: Discussionmentioning

confidence: 99%

“…For this analysis, we used multivariate ordinal logistic regression models, with an ordinal outcome: control (0), early (1), intermediate (2), and late (3) stage AMD. Again, the analyses for each metabolite (adjusted for age, gender, BMI, and AREDS supplementation) were performed for each cohort and meta-analyzed using a fixed-effects model [30]. In these models, the odds ratio provided for each cohort represents the effect size of a one-unit increase (i.e., standard deviation) of the urine metabolite levels on the odds of having a more severe stage of disease.…”

Section: Discussionmentioning

confidence: 99%

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Urinary Mass Spectrometry Profiles in Age-Related Macular Degeneration

Mendez

Gil

Kelly

et al. 2022

JCM

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We and others have shown that patients with different severity stages of age-related macular degeneration (AMD) have distinct plasma metabolomic profiles compared to controls. Urine is a biofluid that can be obtained non-invasively and, in other fields, urine metabolomics has been proposed as a feasible alternative to plasma biomarkers. However, no studies have applied urinary mass spectrometry (MS) metabolomics to AMD. This study aimed to assess urinary metabolomic profiles of patients with different stages of AMD and a control group. We included two prospectively designed, multicenter, cross-sectional study cohorts: Boston, US (n = 185) and Coimbra, Portugal (n = 299). We collected fasting urine samples, which were used for metabolomic profiling (Ultrahigh Performance Liquid chromatography—Mass Spectrometry). Multivariable logistic and ordinal logistic regression models were used for analysis, accounting for gender, age, body mass index and use of AREDS supplementation. Results from both cohorts were then meta-analyzed. No significant differences in urine metabolites were seen when comparing patients with AMD and controls. When disease severity was considered as an outcome, six urinary metabolites differed significantly (p < 0.01). In particular, two of the metabolites identified have been previously shown by our group to also differ in the plasma of patients of AMD compared to controls and across severity stages. While there are fewer urinary metabolites associated with AMD than plasma metabolites, this study identified some differences across stages of disease that support previous work performed with plasma, thus highlighting the potential of these metabolites as future biomarkers for AMD.

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“…LC/MS metabolomics is a new omics approach that analyzes the low-molecular-weight metabolites of a certain organism in a specific physiological period. , It is based on high-throughput mass spectrometry technology, cluster index analysis, and data processing to screen and identify the differential metabolites associated with the disease phenotype. , Compared with other omics approaches, metabolomics is rather new and has already attracted substantial interest in the field of depression biomarkers …”

Section: Introductionmentioning

confidence: 99%

Metabolomics Based on Peripheral Blood Mononuclear Cells to Dissect the Mechanisms of Chaigui Granules for Treating Depression

Huang

Wang

et al. 2022

ACS Omega

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Chaigui granules were a traditional Chinese medicine (TCM) preparation with antidepressant effects derived from a famous antidepressant prescription. It was of great significance to clarify the antidepressant mechanism of Chaigui granules for the clinical application of this drug. In this study, a chronic unpredictable mild stress (CUMS) depression model was successfully established, and behavioral indicators were used to evaluate the antidepressant effect. Second, the CD4+, CD8+, and CD4+/CD8+ levels were detected in peripheral blood. Meanwhile, the amount of inflammatory cytokines was determined in serum. Correspondingly, LC/MS-based peripheral blood mononuclear cell (PBMC) metabolomics was used to investigate vital metabolic pathways participating in the antidepressive effects of Chaigui granules. Finally, bioinformatics technology was further employed to discover the potential antidepressant mechanism of Chaigui granules regulating the immune system. The results suggested that the administration of Chaigui granules significantly improved CUMS-induced depressive symptoms. Chaigui granules could improve immune function by regulating T lymphocyte subsets, increasing anti-inflammatory cytokine levels of IL-2 and IL-10, and reducing pro-inflammatory cytokine levels of TNF-α, IL-1β, and IL-6. In addition, metabolomics results of PBMCs showed that Chaigui granules improved 14 of the 25 potential biomarkers induced by CUMS. Metabolic pathway analyses indicated that purine metabolism was the critical metabolic pathway regulated by Chaigui granules. Furthermore, correlation analysis indicated that 13 key biomarkers were related to immune-related indicators. The metabolite−gene network of 13 key biomarkers was investigated by using bioinformatics. The investigation showed that 10 targets (5′-nucleotidase ecto; 5′-nucleotidase, cytosolic IB; 5′-nucleotidase, cytosolic II; etc.), mainly belong to the purine metabolism, might be potential targets for Chaigui granules to exert their antidepressant effects by improving immune function impairment. Together, our results suggested that Chaigui granules might exert antidepressant effects by improving immune function and regulating the purine metabolic pathway in PBMCs. This work used PBMCs metabolomics as an entry point to study the antidepressant mechanism of Chaigui granules, which provided a new way to elucidate the mechanism of a traditional Chinese medicine prescription.

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Untargeted metabolomics for uncovering plasma biological markers of wet age-related macular degeneration

Cited by 20 publications

References 65 publications

Evolving treatment paradigms for PCV

Evolving treatment paradigms for PCV

Urinary Mass Spectrometry Profiles in Age-Related Macular Degeneration

Metabolomics Based on Peripheral Blood Mononuclear Cells to Dissect the Mechanisms of Chaigui Granules for Treating Depression

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