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. 2021 Sep 22;10(10):944. doi: 10.3390/biology10100944

Table 1.

Summary of metabolomics-based clinical studies of AMD.

AMD Stage Samples Metabolic Biomarkers/Pathway Analytical Platform Untargeted/TARGETED Study Design References
late AMD (wet) plasma (−) Phe, Tyr, Gln, Asp, His-Arg, Trp-Phe, GCA, GDCA, GUDCA; tyrosine metabolism, sulfur amino acid metabolism, and amino acids related to urea metabolism pathway LC-MS Untargeted case-control [52]
early, intermediate, and late AMD plasma (fasting) acetate, acetoacetate, creatine, dimethyl sulfone, β-hydroxybutyrate, pyruvate, Ala, Gln, His NMR Untargeted cross-sectional [53]
late AMD (wet) plasma (fasting) N-acetyl-L-alanine, N1-methyl-2-pyridone-5-carboxamide, Tyr, Phe, Arg, Met, palmitoylcarnitine, isomaltose, hydrocortisone, biliverdin GC-MS, LC-MS Untargeted case-control [54]
early, intermediate, and late AMD plasma (fasting) linoleoyl-arachidonoyl-glycerol (18:2/20:4), stearoyl-arachidonoyl-glycerol (18:0/20:4), oleoyl-arachidonoyl-glycerol (18:1/20:4), 1-palmitoyl-2-arachidonoyl-GPC (16:0/20:4n6), 1-stearoyl-2-arachidonoyl-GPC (18:0/20:4), adenosine; diacylglycerol, glycerophospholipids pathway, purine metabolism LC-MS Untargeted cross-sectional [55]
late AMD (wet) plasma (−) L-oxalylalbizziine, isopentyl β-D-glucoside, LysoPC(P-18:0), LysoPC(P-18:1(9Z)), LysoPC(16:1(9Z)), 1-Lyso-2-arachidonoyl-phosphatidate, 9-hexadecenoylcarnitine, heptadecanoylcarnitine, 11Z-octadecenylcarnitine, L-palmitoylcarnitine, stearoylcarnitine, N-ornithyl-L-taurine; carnitine shuttle pathway, bile acid biosynthesis pathway LC-MS Untargeted [56]
early, intermediate, and late AMD plasma (fasting) taurine, β-citrylglutamate, serotonin, N-acetylmethionine, Asp, hypotaurine, N-acetylasparagine, S-adenosylhomocysteine, maltotriose, maltose, nicotinamide, adenosine, cytidine, guanine, inosine, hypoxanthine, adenine, isoleucylglycine, 1-stearoyl-2-oleoyl-GPS(18:0/18:1), PE, PC, sphingosine, 1-(1-enyl-palmitoyl)-GPE (P-16:0), 14-HDoHE/17-HDoHE, 12-HETE, sphinganine, 1-(1-enyl-oleoyl)-GPE (P-18:1), 1-(1-enyl-stearoyl)-GPE (P-18:0); glycerophospholipid, purine, taurine and hypotaurine, and nitrogen metabolism LC-MS Untargeted cross-sectional [57]
late AMD (wet) plasma (fasting) Val, Lys, Pro, carnitine, valerylcarnitine, carnosine (Ala-His) LC-MS Targeted (IDQ p180 kit) case-control [58]
early, intermediate, and late AMD plasma, serum (+) HDL and VLDL lipoprotein particles, fatty acids, citrate, Ala, Ile, Leu, Phe, Tyr NMR Untargeted [38]
early, intermediate AMD) serum (non-fasting) Gln, Glu:Gln ratio, glutaminolysis, phosphatidylcholine diacyl C28:1; glutamine pathway LC-MS Targeted (IDQ p180 kit) case-control [59]
late AMD (wet) serum (fasting) lactate, lipoproteins NMR Untargeted [48]
late AMD (wet) serum (−) GPC, LysoPC (18:2), PS (18:0/20:4) LC-MS Untargeted case-control [50]
AMD subtype (PCV) serum (fasting) LPA (18:2), LysoPC (20:4), PC (20:1p/19:1), SM (d16:0/22:2), PAF (35:4), PC (16:0/22:5), PC (18:1/20:4); glycerophospholipid metabolism, ether lipid metabolism, glycerolipid metabolism pathway LC-MS Untargeted(lipidomic) [60]
early, intermediate, and late AMD urine (fasting) 4-hydroxyphenylacetate, formate, s-inositol, sucrose, citrate, Val NMR Untargeted cross-sectional [37]
late AMD (wet) aqueous humor carnitine, deoxycarnitine, N6-trimethyl-L-lysine, cis-aconitic acid, itaconatic acid, mesaconic acid, Gly, betaine, creatine; carnitine-associated mitochondrial oxidation pathway, carbohydrate metabolism pathway, osmoprotection pathway LC-MS/MS Untargeted case-control [61]

Amino acids [Ala: alanine; Arg: arginine; Asp: aspartate; Gln: glutamine; Gly: glycine; His: histidine; Ile: isoleucine; Leu: leucine; Lys: lysine; Met: methionine; Phe: phenylalanine; Pro: proline; Tyr: Tyrosine; Val: valine]. Lipids [GPC: glycerophosphocholine; GPS: glycerophophatidyl-serine; GPE: glycerophosphoryl-ethanolamine; HDL: high-density lipoprotein; HDoHE: hydroxydocosahexaenoic acid; HETE: hydroxyeicosatetraenoic acid; LPA: lysophosphatidic acid; LysoPC: lysophosphatidylcholine; PAF: platelet-activating factor; PC: phosphatidylcholine; PE: phosphatidylethanolamine; PS: phosphatidylserine; SM: sphingomyelin; VLDL: very-low-density lipoprotein]. Cholic acids [GCA: glycocholic acid; GDCA: glycodeoxycholic acid; GUDCA: glycoursodeoxycholic acid]. PCV: polypoidal choroidal vasculopathy. −: not state in the article. +: the study consists of multiple cohorts, samples of several cohorts are collected under fasting, and samples of other cohorts are collected under non-fasting.