Human Plasma Metabolomics Study across All Stages of Age-Related Macular Degeneration Identifies Potential Lipid Biomarkers

Laíns, Inês; Kelly, Rachel S.; Miller, John B.; Silva, Rufino; Vavvas, Demetrios G.; Kim, Ivana K.; Murta, Joaquim; Lasky‐Su, Jessica; Husain, Deeba

doi:10.1016/j.ophtha.2017.08.008

Cited by 84 publications

(116 citation statements)

References 61 publications

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“…34 To our knowledge, there is only one previous report that used a metabolomics approach in describing both glucose and pyruvate concentrations in living human subjects from plasma. 15 Our own AH findings from patients with AMD were consistent with this report.…”

Section: Discussionsupporting

confidence: 91%

Glucose Metabolic Characterization of Human Aqueous Humor in Relation to Wet Age-Related Macular Degeneration

Han

Wei

et al. 2020

Invest. Ophthalmol. Vis. Sci.

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Purpose Energy compromise underpins wet age-related macular degeneration (wAMD) pathogenesis, but the relationship between glucose metabolism and the disease remains unclear. Here, we characterized aqueous humor (AH) to elucidate glucose-related metabolic signatures in patients with wAMD. Methods In total, 25 eyes of 25 patients with wAMD were divided into phakic (15 eyes), pseudophakic (10 eyes), and intravitreal injections of ranibizumab (13 eyes) wAMD groups. Twenty patients with cataract (21 eyes) served as controls. Ultrahigh-performance liquid chromatography tandem mass spectrometry was used to quantitatively characterize AH. Results Twenty-one metabolites related to glucose metabolism were identified in AH from 45 patients. Tricarboxylic acid (TCA)-related metabolic substrates, including citrate, were detected in AH and were significantly increased in AMD ( P < 0.01) and AMD pseudophakic groups ( P < 0.05). In contrast, α -ketoglutarate levels were decreased in the AMD group ( P < 0.05). The α -ketoglutarate/citrate ratio was significantly decreased, corresponding to 71.71% and 93.6% decreases in the AMD (phakic and pseudophakic) groups as compared with controls ( P < 0.001), revealing a significant positive correlation with glutamine. A lower mean glutamine and higher glutamate level were detected in AMD cases compared with controls. No significant differences were observed for lactic acid or other Krebs cycle metabolites. Intravitreal injection significantly alleviated mean central foveal thickness but did not significantly alter metabolites. Conclusions Compromised glucose TCA cycle and altered glutamine metabolism are implicated in the AH metabolism in wAMD. These findings highlight potential treatments for alleviating wAMD from a metabolic perspective.

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Section: Discussionsupporting

confidence: 91%

Glucose Metabolic Characterization of Human Aqueous Humor in Relation to Wet Age-Related Macular Degeneration

Han

Wei

et al. 2020

Invest. Ophthalmol. Vis. Sci.

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“…We would also like to clarify that MS and nuclear magnetic resonance spectroscopy (NMR) are complementary methods, and therefore do not necessarily assess the same metabolites. 1 MS is more sensitive, and able to detect much smaller metabolites than NMR; thus, there are several metabolites that are detectable using MS and not using NMR, which may account for the differences observed in our 2 assessments. 2 Regarding the question of the appropriate sample size for this study, it is important to recognize that in metabolomics many factors complicate sample size determination, including its characteristically untargeted approach.…”

Section: Bingqian Liu MD Phd Shida Chen Md Phdmentioning

confidence: 87%

Re: Laíns et al.: Human plasma metabolomics study across all stages of age-related macular degeneration identifies potential lipid biomarkers ( Ophthalmology . 2018;125:245-254)

Liu

Chen

2018

Ophthalmology

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“…Nevertheless, the role of lipids in the pathogenesis of AMD has been seen in a genome-wide association study 16 and study of human plasma metabolomics by our group also suggests that the most significant metabolites associated with AMD are involved in lipid metabolism, especially the glycerophospholipid pathway. 17 In this study, we explore the association of dietary intake of FA (total fat, and fat divided into trans fat, saturated fat, polyunsaturated FA (PUFA), and monounsaturated FA (MUFA) with the early, intermediate, and advanced stages of AMD.…”

mentioning

confidence: 99%

Higher Intake of Polyunsaturated Fatty Acid and Monounsaturated Fatty Acid is Inversely Associated With AMD

Roh

Shin

Providência

et al. 2020

Invest. Ophthalmol. Vis. Sci.

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Citation: Roh M, Shin HJ, Laíns I, et al. Higher intake of polyunsaturated fatty acid and monounsaturated fatty acid is inversely associated with AMD. Invest Ophthalmol Vis Sci. 2020;61(2):20. https://doi.org/10.1167/iovs.61.2.20 PURPOSE. To evaluate the association between dietary fat intake and the presence of AMD. METHODS.Cross-sectional, observational study with cohorts prospectively recruited from the United States and Portugal. AMD was diagnosed based on color fundus photographs with the AREDS classification. A validated food frequency questionnaire was used to calculate the percent energy intake of trans fat, saturated fat, monounsaturated fatty acid (MUFA), and polyunsaturated fatty acid (PUFA). Odds ratio (OR) and 95% confidence intervals for quintile of amount of FA were calculated. Multiple logistic regression was used to estimate the OR. RESULTS.We included 483 participants, 386 patients with AMD and 97 controls. Higher intake of trans fat was associated with a 2.3-fold higher odds of presence of AMD (P for trend = 0.0156), whereas a higher intake of PUFA (OR, 0.25; P for trend = 0.006) and MUFA (OR, 0.24; P for trend < 0.0001) presented an inverse association. Subgroup analysis showed that higher quintile of trans fat was associated with increased odds of having intermediate AMD (OR, 2.26; P for trend = 0.02); and higher quintile of PUFA and MUFA were inversely associated with intermediate AMD (OR, 0.2 [P for trend = 0.0013]; OR, 0.17 [P for trend < 0.0001]) and advanced AMD (OR, 0.13 [P for trend = 0.02]; OR, 0.26 [P for trend = 0.004]). Additionally, a statistically significant effect modification by country was noted with inverse association between MUFA and AMD being significant (OR, 0.04; P for trend < 0.0001) for the Portugal population only. CONCLUSIONS.Our study shows that higher dietary intake of trans fat is associated with the presence of AMD, and a higher intake of PUFA and MUFA is inversely associated with AMD.A MD is the third leading cause of blindness worldwide. 1The mechanism of AMD is still poorly defined, although multifactorial risk factors such as age, race, family history or genetic factors, and smoking have been shown to increase the risk for development of the AMD. 2 Currently, recommendations from the National Eye Institute for lifestyle modification are to avoid smoking, exercise regularly, maintain a normal blood pressure, and control cholesterol levels. As

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Human Plasma Metabolomics Study across All Stages of Age-Related Macular Degeneration Identifies Potential Lipid Biomarkers

Cited by 84 publications

References 61 publications

Glucose Metabolic Characterization of Human Aqueous Humor in Relation to Wet Age-Related Macular Degeneration

Glucose Metabolic Characterization of Human Aqueous Humor in Relation to Wet Age-Related Macular Degeneration

Re: Laíns et al.: Human plasma metabolomics study across all stages of age-related macular degeneration identifies potential lipid biomarkers ( Ophthalmology . 2018;125:245-254)

Higher Intake of Polyunsaturated Fatty Acid and Monounsaturated Fatty Acid is Inversely Associated With AMD

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