Metabolomics and Age-Related Macular Degeneration
Abstract
:1. Introduction
2. Metabolic Processes in the Posterior Eye
2.1. Energy Sources in the Retina
2.2. Lipofuscin Accumulation in the RPE
2.3. Sub-RPE Accumulations
2.3.1. Lipid Accumulation
2.3.2. Advanced Glycation End Product Accumulation
2.3.3. Drusen Accumulation and Development
2.3.4. Trace Metal Homeostasis
2.4. Choroid-BrM-RPE Interaction
3. Metabolomics in AMD
3.1. Introduction into Metabolomics
3.2. Retinal Tissues
3.3. RPE Cells
3.4. RPE Cells and the Retina
3.5. Biofluids
4. Alternative Approaches for AMD Metabolomics Studies
4.1. Tears
4.2. Vitreous and Aqueous Humor
4.3. In vivo Imaging
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Subjects and Biofluid Used | Number of Identified Metabolites | Metabolite Separation Method (Chromatography) | Detection Instrument Used | Reference |
---|---|---|---|---|
Mouse eye lysates | Not reported | Imtakt Scherzo SM-18 150 × 2 mm column Agilent 1200 capillary LC | Agilent 6538 UHD-QTOF MS (ESI+/ESI-) | [36] |
Mouse eye lysates | 203 | XBridge C18 column (3.5 µm, 135 Å, 150 mm × 1.0 mm) Agilent 1260 HPLC | Agilent 6538 UHD Accurate Mass Q-TOF (ESI+) | [118] |
Human serum (NVAMD); Mouse eye lysates | Not reported | Aeris Peptide XB-C18 column (3.6 µm, 100 × 2.10 mm) Phenomenex HPLC | Untargeted: Thermo Scientific LTQ Velos Orbitrap (ESI+/ESI-) Targeted: Thermo Scientific LXQ (ESI-) | [124] |
hfRPE cells; Mouse retina; Apical/basal secretomes | 202 (101 in medium; 53 changed substantially) | Ethylene bridged hybrid Amid column (1.7 µm, 2.1 mm × 150 mm) Agilent 1260 HPLC | AB Sciex QTrap 5500 (MRM) | [125] |
Human plasma (NVAMD) | 1168 (94 differed significantly) | Hamilton PRPX-110S (2.1 cm × 10 cm) anion exchange column | Thermo LTQ-FT spectrometer (ESI+) | [126] |
Human plasma (NVAMD) | 864 (10 differed significantly) | Acquity HSS T3 UPLC column (1.8 µm, 2.1 × 100 mm) Agilent 1290 Infinity UHPLC | AB SCIEX Triple 6600 TOF (ESI+/ESI-) | [127] |
Human plasma | 1188 spectra (30 low-Mw metabolites) | N/A | NMR: Bruker Avance DRX 500 spectrometer (300 K) operating at 500.13 MHz for protein, with a 5 mm TXI probe | [128] |
Human plasma (nonexudative) | 698 endogenous (87 associated with AMD) | C18 (acidic positive and basic negative ionization); HILIC (negative ionization) Waters ACQUITY ultra-UPLC (Metabolon, Inc.) | Thermo Scientific Q-Exactive (HESI-II), Orbitrap mass analyzer | [129] |
WT mouse plasma (MS) and urine (NMR) | MS: 309 NMR: 47 | Polar and nonpolar lipids: ACQUITY BEH C8 column (1.7 µm, 100 × 2.1 mm) Simadzu Nexera X2 UHPLC Hydrophilic metabolites: Atlantis HILIC column (3 µm, 150 × 2 mm) Shimadzu Nexera X2 UHPLC Additional polar metabolites: Phenomenex Luna NH2 column (150 × 2.0 mm) ACQUITY UHPLC | Polar and nonpolar lipids: Thermo Scientific Exactive Plus Orbitrap MS (ESI+) Hydrophilic metabolites: Thermo Fisher Scientific Q Exactive hybrid quadrupole Orbitrap MS (ESI+) Additional polar metabolites: AB SCIEX 5500 QTRAP MS (ESI- and MRM) NMR: Bruker Avance 600 spectrometer | [130] |
Human plasma (NVAMD) | 159 features differed (39 with medium to high confidence) | Hamilton PRP-X110S, 2.1 × 10 cm (anion exhchange) a Higgins Analytical C18 column, 2.1 × 10 cm (reverse phase) a | Thermo Scientific LTQ Velos Orbitrap MS (ESI+) | [131] |
Reference | Biofluid | Comparison | Metabolomic Technique Employed | Definitively Identified Metabolites | Level in AMD Cohort Compared to Controls |
---|---|---|---|---|---|
[124] | Blood serum | NVAMD patients (n = 22) and age-matched control patients (n = 22) | LC-MS | Docosahexaenoic acid | Lower |
Amino acids | Higher | ||||
Prostaglandin G2 | Higher NS | ||||
[159] | Blood plasma | Intermediate AMD (drusen), late AMD (GA and CNV) (n = 77) and non-AMD control patients (n = 75) | HPLC and GC-negative-ion chemical ionization (NICI)-MS | Cystine Isofurans | Higher NS |
[126] | Blood plasma | NVAMD patients (n = 26) and age-matched control patients (n = 19) | LC- Fourier transform MS (FTMS) | Acetylphenylalanine | Higher |
Dipeptide; Tripeptides (modified cysteine and alanine a) | |||||
Sethoxydim | |||||
Tripeptides b | |||||
Tripeptides (acetyltryptophana) | |||||
Flavones; halofenozide | |||||
Glycocholic acid | Lower | ||||
Vitamin D-related metabolites; phytochemicals b | |||||
Glycodeoxycholic acid+H+; Glycoursodeoxycholic acid+H+ | |||||
Glycodeoxycholic acid+Na+; Glycoursodeoxycholic acid+Na+ | |||||
Sencrassidol | |||||
Didemethylsimmondsin | |||||
Dipeptides b | |||||
[127] | Blood plasma | NVAMD patients (n = 20) and age-matched control patients (n = 20) | UPLC-TOF-MS | N-Acetyl-l-alanine | Higher |
l-Tyrosine | |||||
l-Phenylalanine | |||||
l-Methionine | |||||
l-Arginine | |||||
Isomaltose | |||||
Ν1-Methyl-2-pyridone-5-carboxamide | Lower | ||||
l-Palmitoylcarnitine | |||||
Hydrocortisone | |||||
Biliverdin | |||||
[167] | Blood serum | NVAMD patients (n = 20), PCV patients (n = 20), and age-matched controls (n = 20) | UPLC-QTOF-MS | Glycerophospholipids c | Higher |
Phosphatidylcholine | |||||
Covalently modified amino acids c | |||||
Di/tri-peptides c | |||||
Tripeptides c | |||||
ω-3 and ω-6 PUFAs c | |||||
Pinolenic acid | |||||
Docoxahexaenoic acid | |||||
Eicosatetraenoic acid | |||||
Carnitine sp. c | |||||
[129] | Blood plasma | AMD patients (n = 314) and age-matched controls (n = 82), both across two locations | HILIC- and UPLC-MS | Creatine d | Higher |
Oleic acid d | Higher f | ||||
N(CH3)3 choline HDL d | |||||
Acetate d | |||||
Dimethylsulfone d | |||||
Pyruvate d | Higher g | ||||
Glutamine e | |||||
Unsaturated F.A. e | |||||
Unsaturated F.A. LDL + VLDL e | |||||
Unsaturated F.A. d | Lower f | ||||
Unsaturated F.A. LDL + VLDL d | |||||
Histidine d | Lower h | ||||
Acetoacetate d | |||||
β-hydroxybutyrate d | |||||
Unsaturated F.A. LDL + VLDL e | Lower f | ||||
Glutamine e | Lower g | ||||
Histidine e | |||||
CH2CH2COOR F.A. e | |||||
CH2CH2C=C F.A. e | |||||
Albumin lysil e | |||||
Alanine e | Lower h | ||||
Histidine e | |||||
Glyceryl C1,3H’ e | |||||
[128] | Blood plasma | AMD patients (n = 89) and age-matched control patients (n = 30) | NMR | N2-methylguanosine | Higher |
1-Stearoyl-2-oleoyl GPC | Lower NS | ||||
1-Linoleoyl-2-arachidonoyl GPC | Lower | ||||
Stearoyl-arachidonoyl glycerol | |||||
Oleoyl-olyeol-glycerol | |||||
Dihomo-linolenoyl carnitine | |||||
1-Stearoyl-2-arachidonoyl GPC | |||||
Linoleoyl-linolenoyl glycerol | |||||
1-Stearoyl-2-linoleoyl-GPI f | |||||
Oleoyl-linoleoyl-glycerol | |||||
Oleoylcarnitine | |||||
Ximenoylcarnitine | |||||
1-Stearoyl-2-arachidonoyl GPI i | |||||
[131] | Blood plasma | NVAMD patients (n = 100) and control patients (n = 192) | LC-MS and LC-MS/MS | l-Oxalylalbizziine j | Higher |
Isopentyl beta-d-glucoside j | |||||
LysoPC(P-18:0) j | |||||
LysoPC(P-18:1(9Z)) j | |||||
LysoPC(16:1(9Z)) j | |||||
Darunavir j | |||||
Bepridil j | |||||
912-Hexadecadienoylcarnitine j | |||||
456-Trimethylscutellarein 7-glucoside j | |||||
1-Lyso-2-arachidonoyl-phosphidate j | |||||
Americanin B j | |||||
Corchoroside A j | |||||
N-Ornithyl-l-taurine j | |||||
Lyciumoside III j | Lower | ||||
Phosphatidylethanolamine f,j | |||||
Phytosphingosine j | |||||
Lenticin j | |||||
9-Hexadecenoylcarnitine k | Higher | ||||
Heptadecanoyl carnitine k | |||||
11Z-Octadecenylcarnitine k | |||||
l-Palmitoylcarnitine k | |||||
Stearoylcarnitine k | |||||
[168,169] | Blood serum and urine | Neovascular and nonexudative AMD patients (n = 104) l | NMR | Arginine | Higher m,NS |
Glucose | Lower m,NS | ||||
Lactate | |||||
Glutamine | |||||
Reduced glutathione |
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Brown, C.N.; Green, B.D.; Thompson, R.B.; Den Hollander, A.I.; Lengyel, I.; On behalf of the EYE-RISK consortium. Metabolomics and Age-Related Macular Degeneration. Metabolites 2019, 9, 4. https://doi.org/10.3390/metabo9010004
Brown CN, Green BD, Thompson RB, Den Hollander AI, Lengyel I, On behalf of the EYE-RISK consortium. Metabolomics and Age-Related Macular Degeneration. Metabolites. 2019; 9(1):4. https://doi.org/10.3390/metabo9010004
Chicago/Turabian StyleBrown, Connor N., Brian D. Green, Richard B. Thompson, Anneke I. Den Hollander, Imre Lengyel, and On behalf of the EYE-RISK consortium. 2019. "Metabolomics and Age-Related Macular Degeneration" Metabolites 9, no. 1: 4. https://doi.org/10.3390/metabo9010004