Metabolomics in Retinal Diseases: An Update
Abstract
:Simple Summary
Abstract
1. Introduction
2. Metabolomics: Brief Overview
3. Metabolomics: Technological Advances
3.1. Mass Spectrometry
3.2. Nuclear Magnetic Resonance (NMR) Spectroscopy
4. Metabolomics in Retinal Diseases
4.1. Age-Related Macular Degeneration (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] |
4.2. Diabetic Retinopathy (DR)
DR Stage | Samples | Metabolic Biomarkers/Pathway | Analytical Platform | Untargeted/Targeted | Study Design | References |
---|---|---|---|---|---|---|
pre-DR, NPDR, PDR | plasma (−) | pyruvate, Asp, glycerol, cholesterol | GC-MS | Untargeted | − | [84] |
NPDR | plasma (−) | 2-deoxyribonic acid, 3,4-dihydroxybutyric acid, erythritol, gluconic acid, ribose; pentose phosphate pathway | GC-MS | Untargeted | case-control | [81] |
NPDR | plasma (−) | 15-oxo-ETE, 4-HDoHE, 11-HEPE, LTB4, PGD2, RvD2, PGD3, PGF2α, 5,6-DiHETE, 8-HDoHE, 5-oxo-ETE, RvD1, 7-HDoHE, 6R-LXA4, 15d-PGJ2, PGJ2, 10-HDoHE, PGE3 | LC-MS/MS | Targeted (eicosanoids) | − | [85] |
NPDR, PDR | plasma (−) | Glu, Gln, Gln/Glu | GC-MS, LC-MS | Untargeted | − | [71] |
PDR | plasma (fasting) | fumaric acid, uridine, acetate, cytidine | LC-MS | Untargeted | case-control | [86] |
NPDR, PDR | plasma (−) | Arg, citrulline, glutamic γ-semialdehyde, dehydroxycarnitine, carnitine | LC-MS | Untargeted | case-control | [87] |
NPDR, PDR | plasma, serum (−) | 2,4-DHBA, 3,4-DHBA, ribonic acid, ribitol, the triglycerides 50:1 and 50:2 | GC-MS, LC-MS | Untargeted | cross-sectional | [88] |
NPDR | serum (−) | ribitol, GPC, UDP-Glc-NAc, fructose-6-phosphate | NMR | Untargeted | − | [89] |
NPDR, PDR | serum (−) | dimethylarginine, Trp, Pro, PC, kynurenine, propionylcarnitine, butyrylcarnitine, hexose | LC-MS | Targeted (IDQ p180 kit) | cross-sectional | [90] |
NPDR, PDR | serum (fasting) | 12-HETE, 2-piperidone | GC-MS, LC-MS | Untargeted | − | [80] |
mild DR | Serum (−) | Cer(d18:1/24:0), ChE 20:3, ChE 20:4, ChE 22:6, DG(16:0_18:2), DG(16:1_18:2), DG(18:2_20:4), DG(18:2_22:6), FA(14:0), FA(16:0) | LC-MS | Untargeted (lipidomic) | − | [91] * |
NPDR, PDR | serum (fasting) | linoleic acid, nicotinamide, ornithine, phenylacetylglutamine | LC-MS | Targeted | case-control | [72] |
NPDR, PDR | vitreous humor | 5-HETE, CYP-derived epoxyeicosatrienoic acids | LC-MS/MS | Targeted (lipidomic) | − | [92] |
PDR | vitreous humor | galactitol, ascorbic acid, lactate | NMR | Untargeted | − | [93] |
PDR | vitreous humor | Arg, Pro, Met, allantoin, citrulline, ornithine, octanoylcarnitine, decanoylcarnitine; arginine, proline, acylcarnitine metabolism pathway | LC-MS/MS | Untargeted | − | [82] |
PDR | vitreous humor | pyruvate, inosine, hypoxanthine, urate, allantoate, pentose phosphates, xanthine; glucose metabolism, purine metabolism, pentose phosphate pathway | LC-MS | Untargeted | − | [83] |
PDR | vitreous humor | 5-HETE, 12-HETE, 20-HETE, 20-COOH-AA | LC-MS/MS | Targeted (eicosanoid) | − | [94] |
PDR | vitreous humour | Pro, pyruvate, lactate, allantoin, creatine, dimethyl glycine, N-acetyl serine, succinate, α-ketoglutarate | LC-MS/MS | Untargeted | cross-sectional | [95] |
PDR | vitreous, aqueous humor | CysSSH, Cys, GSSSG, cystine | LC-MS/MS | Targeted (polysulfides) | − | [96] |
PDR | vitreous, aqueous humor | d-2,3-dihydroxypropanoic acid, isocitric acid, fructose 6-phosphate, lactate; pyroglutamic acid, pyruvate; gluconeogenesis, ascorbate-aldarate metabolism, valine–leucine–isoleucine biosynthesis, and arginine–proline metabolism pathway | GC-MS | Untargeted | − | [97] |
DR | aqueous humor | His, Thr, Gln, Asn, dimethylamine, lactate, succinate, 2-hydroxybutyrate; alanine, aspartate, and glutamate metabolic pathway | NMR | Untargeted | − | [98] |
4.3. Retinopathy of Prematurity (ROP)
Disease | Samples | Metabolic Biomarkers/Pathway | Analytical Platform | Untargeted/Targeted | Study Design | References |
---|---|---|---|---|---|---|
ROP | plasma (−) | N1-methyl-2-pyridone-5-carboxamide, biliverdin, linoleic acid, 4-guanidinobutyric acid, adenosine, thioetheramide-PC, citrulline, GCDC, cis-9-palmitoleic acid, sunitinib, vanillin, trehalose, 1-aminocyclopropanecarboxylic acid | LC-MS | Untargeted | − | [108] |
ROP | Blood (−) | Gly, Glu, Leu, Ser, Val, Trp, piperidine, citrulline, malonyl carnitine, homocysteine | LC-MS | Targeted | − | [109] |
4.4. Glaucoma
Disease | Samples | Metabolic Biomarkers/Pathway | Analytical Platform | Untargeted/ Targeted | Study Design | References |
---|---|---|---|---|---|---|
POAG | plasma (−) | palmitoylcarnitine, hydroxyergocalciferol, C17 sphinganine, ergostanol | LC-MS/MS | Untargeted | case-control | [125] * |
POAG | plasma (fasting) | octadecadienyl-carnitine (C18:1), methionine sulfoxide, propionyl-carnitine, PC (34:2), PC (34:4), PC (36:4) | LC-MS | Targeted (IDQ p180 kit) | − | [126] |
POAG | plasma (fasting) | nicotinamide, hypoxanthine, xanthine, 1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, cystathionine, N-acetyl-L-leucine, Arg, rac-glycerol 1-myristate, 1-oleoyl-rac-glycerol | LC-MS | Untargeted | − | [127] |
PACG | plasma (fasting) | myristic acid, stearic acid, oleic acid, arachidic acid, eicosenoic acid, eicosadienoic acid, eicosatrienoic acid, AA, eicosapentaenoic acid, docosapentaenoic acid, erucic acid, docosatetraenoioc acid, docosahexaenoic acid, tetracosanoic acid | LC-MS/MS | Targeted (FFAs, lipids) | cross-sectional | [128] |
PACG | serum (fasting) | palmitoleic acid, linoleic acid, γ-linolenic acid, AA | GC-MS | Targeted (FFAs) | − | [129] |
POAG | serum (fasting) | Gly, Gly-Pro, Asp-Pro, citric acid, Lys, Glu-Ala, MHPG, hypoxanthine, 17-hydroxypregnenolone sulfate, 3α,7α-dihydroxycholanoic acid | GC-MS | Untargeted | − | [116] |
OAG | aqueous humor | diacylglycerophosphocholines and 1-ether, 2-acylglycerophosphocholines, SM (d18:2/16:0), SM (d18:1/18:0) | LC-MS | Untargeted (lipidomic) | − | [130] * |
POAG | aqueous humor | taurine, spermine, creatinine, carnitine, propionylcarnitine, acetylcarnitine, Gln, Gly, Ala, Leu, Ile, hydroxyl-proline, acetyl-ornithine, SM (C18:1), LysoPC (C28:1), PC (34:1), PC (36:2), PC (36:4), PC (38:4), PC (32:1) | FIA-MS/MS | Untargeted (lipidomic) | case-control | [131] * |
PCG | aqueous humor | Gly, Phe, urea | GC-MS | Untargeted | − | [132] |
POAG, PEXG | aqueous humor | Arg, Lys, Gln, Tyr, His, creatine, 2,4-diacetamido-2,4,6-trideoxy-beta-l-altrose, 5-hydroxypentanoate, N(6)-acetonyllysine, propylene glycol, 1-aminocyclopropane-1-carboxylate | NMR, LC-MS/MS | Untargeted | − | [117] |
POAG | aqueous humor | biotin, glucose-1-phosphate, methylmalonic acid, N-cyclohexylformamide, sorbitol, spermidine, 2-mercaptoethanesulfonic acid, galactose, mannose, talose, erythronolactone, dehydroascorbic acid | GC-MS | Untargeted | case-control | [133] |
POAG | aqueous humor | Lys, Arg, Cys, Gly, Gln, Phe, anthranilate, ascorbate, 4-hydroxybenzoate, myo-inositol, acetate, propylene glycol, 2-hydroxy-butyrate, creatine, choline, 4-aminobutanoate, isopropanol | NMR, LC-MS/MS | Untargeted | − | [118] |
POAG | aqueous humor | betaine, taurine, Glu | NMR | Untargeted | cross-sectional | [65] |
POAG | aqueous humor | adenine, N-acetyl alanine, hypoxanthine, Lys, Phe-Glu, nicotinamide, 2-aminobutyraldehyde, acetate | LC-MS | Targeted | − | [134] |
POAG | aqueous humor, plasma (fasting) | cyclic AMP, methylbenzoic acid, 3′-sialyllactose, N-lactoyl-phenylalanine | LC-MS | Targeted | − | [115] |
POAG | tear | Ala, Arg, Gln/Lys, Leu/Ile/Pro-OH, Met, Phe, Pro, Val, acetylcarnitine, LysoPC (C22:0), LysoPC (C24:0) | DI-MS | Targeted | − | [135] |
4.5. Retinitis Pigmentosa (RP)
5. Discussion
5.1. Samples
5.2. Study Design
5.3. Differential Metabolites/Biomarkers and Pathway
6. Conclusions and Perspectives
Author Contributions
Funding
Conflicts of Interest
References
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Disease | Common Differential Metabolites/Biomarkers |
---|---|
AMD-DR | 12-HETE, acetate, Arg, Asp, carnitine, creatine, cytidine, Gln, GPC, His, hypoxanthine, inosine, lactate, Met, nicotinamide, PC, Pro, pyruvate |
AMD-Glaucoma | acetate, adenine, Ala, Arg, betaine, carnitine, creatine, Gln, Gly, His, hypoxanthine, Ile, Leu, Lys, Met, nicotinamide, palmitoylcarnitine, Phe, Pro, taurine, Tyr, Val |
DR-Glaucoma | acetate, Arg, carnitine, creatine, Cys, Gln, Glu, His, hypoxanthine, linoleic acid, Met, nicotinamide, Pro, propionylcarnitine, xanthine |
AMD-DR-Glaucoma | acetate, Arg, carnitine, creatine, Gln, His, hypoxanthine, Met, nicotinamide, Pro |
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Li, X.; Cai, S.; He, Z.; Reilly, J.; Zeng, Z.; Strang, N.; Shu, X. Metabolomics in Retinal Diseases: An Update. Biology 2021, 10, 944. https://doi.org/10.3390/biology10100944
Li X, Cai S, He Z, Reilly J, Zeng Z, Strang N, Shu X. Metabolomics in Retinal Diseases: An Update. Biology. 2021; 10(10):944. https://doi.org/10.3390/biology10100944
Chicago/Turabian StyleLi, Xing, Shichang Cai, Zhiming He, James Reilly, Zhihong Zeng, Niall Strang, and Xinhua Shu. 2021. "Metabolomics in Retinal Diseases: An Update" Biology 10, no. 10: 944. https://doi.org/10.3390/biology10100944