Amino Acids Metabolism in Retinopathy: From Clinical and Basic Research Perspective
Abstract
:1. Introduction
2. Metabolomics-Based Amino Acid Metabolism in Retinopathy
2.1. Amino Acids in Retinopathy by Analysis of Metabolomics
2.2. Amino Acids- Related Metabolic Pathways in Retinopathy
2.3. Potential Effects of Metabolites in Retina
3. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Species | Samples | Subjects | Platforms | Criteria | Differential Metabolites | Study |
---|---|---|---|---|---|---|
Human | Plasma | 42 DR/ 32 NDR | UPLC-MS | Fold change (FC) > 1.2 and p < 0.05 | N-Fructosyl isoleucine | Sun et al. (2021) [17] |
N-acetyltryptophan | ||||||
Leucylleucine | ||||||
Kynurenic acid | ||||||
3-Methylhistidine | ||||||
Phenylacetylglutamine | ||||||
21 PDR/ 21 NPDR | Glutamine | |||||
52 PDR/ 72 NPDR/ 59 NDR | UPLC-MS, GC-MS | Variable important in the projection (VIP) > 0.7 | asparagine, aspartic acid, glutamic acid, glutamine, glycine, methionine, pyroglutamic acid | Rhee et al. (2018) [18] | ||
21 PDR/ 21 NDR | UPLC-MS | p < 10 × 10−5, Area under the curve (AUC) ≥ 0.95, VIP > 1 | L-serine, β-alanine, L-Proline, L-Homoserine,4-Hydroxyproline, Ornithine, L-Aspartic acid, L-Glutamine, L-Glutamic acid, L-Methionine, N-Acetylornithine, L-Arginine, N-Acetyl-L-aspartic acid, Citrulline, Phosphoserine | Zhu et al. (2019) [19] | ||
83 DR/ 90 NDR | LC-MS | VIP ≥ 2.0 | arginine, citrulline | Sumarriva et al. (2019) [20] | ||
64 PDR/ 92 NPDR/ 159 NDR | LC-MS | FDR (false-discovery rate) < 0.05 | ↑: arginine, citrulline (DR/ NDR) | Peters et al. (2021) [21] | ||
19 DR/ 14 controls | NMR | p < 0.05 | ↑: leucine, isoleucine, tyrosine, and valine; ↓: histidine, Alanine | Lin et al. (2019) [22] | ||
88 PDR/ 51 controls | UPLC-MS | VIP > 1, FC > 1.2 and < 0.83, FDR = 0.05 | ↑: Pyroglutamic acid, Alpha-N-phenylacetyl-L glutamine | Wang et al. (2022) [23] | ||
Serum | 25 NDR/ 39 DR/ 25 PDR | GC-MS | largest VIP | L-aspartic acid | Li et al. (2011) [24] | |
176 DR/ 329 NDR | LC-MS | p < 0.05 | ↑: asymmetric dimethylarginine (ADMA), L-arginine, symmetric dimethylarginine (SDMA) | Abhary et al. (2009) [25] | ||
689 DR/ 216 control | GC-MS, LC-MS | p < 0.05, FDR < 0.05 | ↑: serine, glycine, arginine, ornithine, citrulline, proline, leucine, isoleucine, and valine | Xuan et al. (2020) [26] | ||
51 PDR/ 123 NPDR/ 143 NDR | LC–MS | p < 0.05 | DR/ NDR: proline, NPDR than NDR: alanine, aspartic acid, and glutamine, arginine, histidine, lysine, methionine, threonine, tryptophan, and tyrosine, PDR than NDR: lysine, methionine, serine, tryptophan, and tyrosine; PDR than NPDR: total dimethylarginine | Yun et al. (2020) [27] | ||
69 DR/ 69 NDR | UPLC-MS | VIP > 1, FC< 0.8 or > 1.2 and FDR < 0.05 | ornithine, phenylacetylglutamine | Zuo et al. (2021) [28] | ||
123 DR/ 116 NDR | Metabolon DiscoveryHD4 | p < 0.05 | cysteine-glutathione disulfide, phenylacetylglutamine, cys-gly (oxidized), N-acetylmethionine glycylvaline, phenylalanine, aspartate, tryptophan, glutamate | Yousri et al. (2022) [29] | ||
Plasma and serum | 228 PDR/ 276 NPDR/ 141 NDR | GC-MS, UHPLC-MS | (Benjamini–Hochberg) BH- adjusted p < 0.05 | alanine and serine | Curovic et al. (2020) [30] | |
666 DR/ 2211 NDR | NMR | p < 0.05 | tyrosine | Quek et al. (2021) [31] | ||
Vitreous humor | 28 PDR/ 22 NDM | GC-MS | VIP > 1 p < 0.05 | alanine, alloisoleucine, creatinine, glutamine, leucine, lysine, ornithine, pyroglutamic acid, phenylalanine, threonine, valine | Wang et al. (2020) [32] | |
51 PDR/ 23 controls | UPLC-MS | VIP > 1 FC >1.2 and < 0.83 FDR = 0.05 | alpha-N-phenylacetyl-L glutamine, pyroglutamic acid | Wang et al. (2022) [23] | ||
22 PDR/ 22 NDM | NMR | p ≤ 0.05 | alanine, valine, glutamine, leucine, isoleucine | Barba et al. (2010) [33] | ||
35 PDR/ 19 NDM | UHPLC-MS | p < 0.05 | citrulline, dimethylglycine, glycine, ornithine, proline, creatine | Tomita et al. (2021) [34] | ||
20 PDR/ 31 NDM | HPLC-MS | p < 0.05 | Methionine, arginine, proline, citrulline, ornithine | Paris et al. (2016) [35] | ||
9 PDR/ 8 controls | UHPLC-MS | p < 0.05 | citrulline, glutamine, N-amidino-L-aspartate, proline, 5-oxoproline | Haines et al. (2018) [36] | ||
Aqueous and humor | 13 DR/ 14 NDR | NMR | VIP > 1.0 p < 0.05 | asparagine, DMA, glutamine, histidine, threonine | Jin et al. (2019) [37] | |
23 PDR/ 25 NDM | GC-MS | VIP > 1.0 p < 0.05 | citrulline | Wang et al. (2020) [32] | ||
Aqueous and vitreous humor | 18 PDR/ 22 controls | LC-MS | p < 0.05 | Cysteine persulfides (CysSSH), cystine, oxidized glutathione trisulfide (GSSSG) | Kunikata et al. (2017) [38] | |
CSF | 19 DR/ 14 controls | NMR | FC > 1.2 or < 0.8, FDR < 0.05 | alanine, leucine, isoleucine, tyrosine, and valine, histidine, | Lin et al. (2019) [22] | |
Urine | 666 DR/ 2211 NDR | NMR | p < 0.05 | Alanine, glutamine | Quek et al. (2021) [31] | |
Fecal samples | 21 PDR/ 14 NDR | UPLC-MS | VIP > 1, p < 0.05 | pyro-L-glutaminyl-L-glutamine, D-proline, N-gamma-L-glutamyl-D-alanine, N-acetyl-L-methionine, L-threo-3-phenylserine, | Zhou et al. (2021) [39] | |
45 PDR/ 90 NDR | UPLC-MS | p < 0.05, VIP> 1, and log2 FC > 1 | tyrosine | Ye et al. (2021) [40] | ||
Rats | Urine | 6 DR rats/6 controls | UPLC-MS | VIP > 1, p < 0.05 | phenylacetylglycine, 5-l-glutamyl-taurine | Wang et al. (2020) [41] |
Zebrafish | Whole body | 50 pdx1−/− zebrafish | UHPLC–MS | p < 0.05 | glutamate, proline, ornithine, tyrosine | Wiggenhauser et al. (2020) [42] |
Species | Samples | Subjects | Platforms | Criteria | Differential Metabolites | Study |
---|---|---|---|---|---|---|
Human | Plasma | Coimbra: 201 AMD /42 controls | NMR | p < 0.05 | Early AMD vs. Controls: creatine; Late vs. Intermediate AMD: histidine | Laíns et al. (2017) [43] |
Boston: 113 AMD /40 controls | p < 0.05 | Early AMD vs. Controls: glutamine; Intermediate vs. Early AMD: glutamine, histidine; Late vs. Intermediate AMD: histidine, alanine | ||||
91 IAMD /100 NVAMD /195 controls | LC-MS | VIP ≥ 2.0 and an p < 0.05 | AMD vs. controls: pyroglutamic acid; NVAMD vs. IAMD: kynurenine | Mitchell et al. (2021) [44] | ||
20 wetAMD /20 controls | UHPLC-MS, QTOF-MS | VIP > 1 and p < 0.05 or 0.05 < p < 0.1 | N-Acetyl-L-alanine, L-Tyrosine, L-Phenylalanine, L-Methionine, L-Arginine, | Luo et al. (2017) [45] | ||
Boston: 149 AMD /47 controls, Coimbra: 242 AMD /53 controls | UHPLC-MS | FDR < 0.05 | Beta-citrylglutamate, N-acetylmethionine, aspartate, N-acetylasparagine, S-adenosylhomocysteine (SAH), isoleucylglycine N-acetylasparagine, beta-citrylglutamate, N-acetylleucine | Laíns et al. (2019) [46] | ||
26 NVAMD /19 controls | LC-FTMS | FDR< 0.05 | Acetylphenylalanine | Osborn et al. (2013) [47] | ||
32 AMD /32 controls | HPLC-MS | p < 0.05 | Homocysteine | Ghosh et al. (2013) [48] | ||
40 AMD /40 controls | LC-MS | 0.6 < FC < 1.4 p < 0.1 | Valine, lysine, proline | Chao et al. (2020) [49] | ||
127 wAMD /50 controls | UHPLC-MS | FC ≥ 2 and FC ≤ 0.5, p < 0.05, VIP ≥ 1 | L-Tryptophan; L-Alanyl-L-Lysine | Deng et al. (2021) [50] | ||
Plasma | 53 AMD /18 controls | UPLC-MS | p < 0.01 | N-acetylglutamine, N-acetylleucine | Mendez et al. (2021) [51] | |
Serum | 72 AMD /72 controls | microLC-MS | sPLSda (to select the most predictive variables from dataset) | (Predictors for non-advanced AMD) glutamine, glutamate:glutamine ratio, glutaminolysis | Kersten et al. (2019) [52] | |
Aqueous humor | 26 wetAMD /20 controls | UHPLC-MS | VIP > 1.0 and p < 0.05 | N6, N6, N6-trimethyl-L-lysine, norleucine, L-phenylalanine, γ-glutamylglutamine, N-acetylhistidine, creatine, N-fructosyl isoleucine, L-proline | Han et al. (2020) [53] | |
Urine | Coimbra cohort: 252 AMD /53 controls | NMR | p < 0.05 | Late AMD vs. Intermediate AMD: valine | Laíns et al. (2019) [54] | |
Boston cohort: 147 AMD /47 controls | p < 0.05 | Intermediate AMD vs. Early AMD: glycine, lysine, tyrosine |
Species | Samples | Subjects | Platforms | Criteria | Differential Metabolites | Study |
---|---|---|---|---|---|---|
Human | Plasma | 58 ROP /25 controls | HPLC-MS/MS | p < 0.05 | Creatinine, citrulline, arginine, and aminoadipic acid, creatinine, and aminoadipic acid | Zhou et al. (2021) [55] |
38 treatment requiring-ROP /23 ROP | UHPLC-MS | FC > 1.5, p < 0.05 | L-Lysine, L-Citrulline, Pro-Thr, L-Glutamine, L-Pyroglutamic acid, L-Tryptophan, Cysteine-S-sulfate, | Zhou et al. (2020) [56] | ||
57 ROP /57 controls | UPLC-MS/MS | VIP > 0.5 | Glutamic acid gamma-methyl ester, Picolinoylglycine, Creatinine, Ornithine, 1-Carboxyethylisoleucine | Yang et al. (2022) [57] | ||
26 ROP /29 controls | LC-MS/MS | p < 0.05 | Arginine, Lysine, aspartic acid, glutamine | Ozcan et al. (2020) [58] | ||
Serum | 87 ROP | NMR | p < 0.05 | Phenylalanine, Lysine | Nilsson et al. (2022) [59] | |
Heel blood | 40 ROP /41 controls | UPLC-MS | VIP > 1 | Glycine, glutamate, leucine, serine, valine, tryptophan, citrulline and homocysteine | Yang et al. (2020) [60] | |
OIR mice | Retina | 10 OIR /10 controls | HPLC-MS/MS | FC > 1.5, p < 0.05. | Dimethylglycine, L-Citrulline, N-Acetyl-L-aspartic acid, L-Alanine, Gly-Glu, D-Proline, Gamma-L-Glutamyl-L-glutamic acid, Creatine, L-Pyroglutamic acid, L-Leucine, L-Aspartate, L-Glutamate, Glycine, L-Citrulline, D-Proline, L-Valine, N-Acetyl-L-aspartic acid ↓, Gamma-L-Glutamyl-L-glutamic acid, Creatine, L-Alanine, L-Aspartate | Zhou et al. (2021) [61] |
Whole eyes | 3 P12 mice /3 P14 mice /4 P17 mice /5 controls | HPLC-MS | p < 0.05 | Arginine, Proline, Citrulline, Ornithine, Lysine | Paris et al. (2016) [35] | |
Rats | Plasma | Four groups, each with 12 individuals: (i) CT1; (ii) HO1; (iii) CT2; (iv) HO2 | GC-MS | p < 0.05, VIP ≥ 1 | HO1/CT1: L-Tyrosine, L-Proline, Ornithine, L-Tryptophan, L-Glutamine, L-Threonine, 4-Hydroxy-L-proline, Glycine, HO2/HO1: L-Proline, L-Alanine, L-Glutamine, L-Tyrosine, Ornithine, L-Threonine, L-Valine, L-Alloisoleucine, L-Lysine, L-Serine, L-Histidine, L-Arginine | Lu et al. (2020) [62] |
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Xia, M.; Zhang, F. Amino Acids Metabolism in Retinopathy: From Clinical and Basic Research Perspective. Metabolites 2022, 12, 1244. https://doi.org/10.3390/metabo12121244
Xia M, Zhang F. Amino Acids Metabolism in Retinopathy: From Clinical and Basic Research Perspective. Metabolites. 2022; 12(12):1244. https://doi.org/10.3390/metabo12121244
Chicago/Turabian StyleXia, Mengxue, and Fang Zhang. 2022. "Amino Acids Metabolism in Retinopathy: From Clinical and Basic Research Perspective" Metabolites 12, no. 12: 1244. https://doi.org/10.3390/metabo12121244