Importance of the Use of Oxidative Stress Biomarkers and Inflammatory Profile in Aqueous and Vitreous Humor in Diabetic Retinopathy
Abstract
:1. Introduction
2. Diabetic Retinopathy
3. Role of Oxidants and Antioxidants in the Eye with Diabetic Retinopathy
3.1. Oxidative Stress and the Damage It Causes to the Eye
3.2. Antioxidants Present in the Tear Film, Aqueous Humor, and Vitreous Humor
4. Ocular Matrices: Tears, Aqueous Humor, and Vitreous Humor
4.1. Tears
- Direct or aspiration: the collection is through microcapillary tubes (MCT) or micropipettes, the tip of the tube is placed in the cul-de-sac for 5 min, in non-stimulated tears (NST), until it forms a lake of tear, then for capillarity tears are absorbed and the sample (5.5–6.5 µL) is transferred immediately into a sterile tube with storage solution or buffer assay to produce a dilution 1:10 and storage at −80 °C. The main advantage is the amount of proteins and biomarkers obtained directly of ocular surface. A disadvantage is the loss of proteins may occur due to incomplete pouring into microvials [75,76].
- Indirect methods: These methods collect the samples of tears through absorbing papers like cellulose sponges or Schirmer test strips (STS), both are invasive techniques. The cellulose sponges are used frequently to analyze inflammatory markers like interleukins and MMP-9 and they are measured by enzyme-linked immunosorbent assay (ELISA) or Luminex technology using tears that were collected with Merocel, Pro-ophta, or Weck-Cel sponges. However, comparative studies with simultaneous measurements of cytokines have shown that Merocel is useful for clinical assess for cytokines/chemokines levels but have the limitation with measures of IL-7 and IL-4 due to protein stability problems with the extraction buffer [75,76,77]. In the case of STS, it may also be used for cytokine analysis assays. For collection of tears, the strip is placed on the inferior fornix of the eye and the patient should close their eyes for 5 min. After completed the time, the patient should open their eyes for remove carefully the strip and then it is collocated into a sterile 1.5 mL tube. Immediately transfer the tube to the laboratory to process later in a bead based multiplex assay or store at −80 °C. With this method the sample contains higher amounts of cellular proteins, lipids, and mucous compared with MCT and the analysis with multiplex provide high sensitivity for analyzing cytokines and other proteins [78].
4.2. Aqueous Humor
4.3. Vitreous Humor
5. Measurement of Biomarkers
5.1. Oxidative Stress: ROS and Relevance in DR
5.2. Inflammation: Cytokines and Relevance in DR
5.3. Apoptosis
6. Metabolic Memory of Oxidative Stress in Diabetic Retinopathy
6.1. DNA Methylation
6.2. Modification of Histones
6.3. Chromatin Remodeling
6.4. Non-Coding RNA
7. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Profile | Biomarker | Matrix | Pathology | Levels | Method | References |
---|---|---|---|---|---|---|
Oxidative Stress | TAC | Aqueous | PDR | 0.55 ± 0.28 µmol Trolox/g * | Radical absorbance capacity assay | [104] |
Vitreous | PDR | 0.19 ± 0.10 µmol Trolox/g * | Radical absorbance capacity assay | [104] | ||
LPO | Vitreous | PDR | Male: 145.8 ± 6.3 µM * | Colorimetric assay | [105] | |
Female: 135.6 ± 10.9 µM * | ||||||
MDA | Tears | DR | 95 µM | Capillary electrophoresis | [106] | |
Aqueous humor | Cataract | 0.1 ± 0.1 µmol/L * | TBARS method | [107] | ||
Vitreous | PDR | Male: 101.3 ± 7.6 nmol/mL * | Colorimetric assay | [105] | ||
Female: 87.6 ± 18.4 nmol/mL * | ||||||
GSH | Tears | DR | 107 µM | Chromatography electrochemical | [24] | |
GPx | Aqueous | Glaucoma | 18.4 ± 2.5 U/mL * | - | [101] | |
Aqueous | Cataract | 6.1 ± 0.6 U/mL * | - | [101] | ||
SOD | Tears | DR | 1–32 U/mg | Spectrophotometry direct | [45,108] | |
Vitreous | PDR | Male: 30.5 ± 2.5 U/mL * | Colorimetric Enzyme assay | [105] | ||
Female: 28.5 ± 3.8 U/mL * | ||||||
8-OHdG | Aqueous | Cataract | 311.6 ± 127.7 µg/mL * | ELISA | [109] | |
Aqueous | Myopic | 212.5 ± 103.2 µg/mL * | ELISA | [109] | ||
8-IPGF | Aqueous | Exfoliation syndrome | 2429 ± 2940 pg/mL * | Immunoassay | [110] | |
Aqueous | Cataract | 529.1 ± 226.8 pg/mL * | Immunoassay | [110] | ||
Aqueous | Diabetic cataract | 624 ± 95.7 pg/mL * | ELISA | [111] | ||
ON | Aqueous humor | PDR | 19.43 ± 8.75 µM * | Colorimetric assay | [95] | |
Vitreous humor | PDR | 0.524 ± 0.27 µM * | spectrophotometric | [112] | ||
T1DM | Griess reaction | |||||
Vitreous humor | PDR | 0.383 ± 0.17 µM * | spectrophotometric | [112] | ||
T2DM | Griess reaction | |||||
L-tyrosine | Tears | DR | 45 µM | Chromatography electrochemical | [24] | |
L-cysteine | Tears | DR | 48 µM | Chromatography electrochemical | [24] | |
Ascorbic acid | Tears | DR | 665 µM | Chromatography electrochemical | [24] | |
Uric acid | Tears | DR | 328 µM | Chromatography electrochemical | [24] | |
Inflammatory | IL-1β | Tears | DR | 16.7 ± 3.2 pg/mL * | Multiplex assay Bio-Plex system | [113] |
IL-6 | Tears | DR | 63.3 ± 12.3 pg/mL * | Multiplex assay | [113] | |
Bio-Plex system | ||||||
Tears | DED | 26.25 ± 5.20 pg/mL * | Multiplex bead assay | [114] | ||
Aqueous humor | DR | 40.64 ± 16.52 pg/mL * | Multiplex bead immunoassay | [115] | ||
Aqueous humor | PDR | 37.19 pg/mL (3.992–4577.38) ** | Immunology Multiplex Assay | [83] | ||
Vitreous fluid | PDR progression | 347.2 pg/mL (26.2–758.6) ** | ELISA | [116] | ||
Vitreous fluid | DR | 42.29 ± 10.94 pg/mL * | ELISA | [117] | ||
Vitreous | DR | 64.2 ± 10.4 pg/mL * | Immunoassay | [118] | ||
IL-8 | Aqueous humor | DR | 42.20 ± 33.03 pg/mL * | Multiplex bead immunoassay | [115] | |
Aqueous humor | PDR | 25.28 pg/mL (13.21–184.62) ** | Immunology Multiplex Assay | [83] | ||
Aqueous humor | PDR | 76.55 ± 10.88 pg/mL * | ELISA | [119] | ||
Vitreous humor | PDR | 63.55 ± 10.74 pg/mL * | ELISA | [119] | ||
IL-10 | Aqueous humor | DR | 0.24 ± 0.16 pg/mL * | Multiplex bead immunoassay | [115] | |
Aqueous humor | Fuchs’ uveitis | 11.70 ± 6.60 pg/mL * | ELISA | [120] | ||
Aqueous humor | Behcet’s uveitis | 7.23 ± 1.73 pg/mL * | ELISA | [120] | ||
Vitreous humor | PDR | 224.789 ± 43.801 pg/mL * | ELISA | [121] | ||
Vitreous | DR | 4.43 ± 0.4 pg/mL * | Immunoassay | [118] | ||
IL-17A | Tears | DED | 454.67 ± 37.70 pg/mL * | Multiplex bead analysis | [114] | |
TNF-α | Tears | NPDR | 1.2–5.5 pg/mL | ELISA | [122] | |
Tears | PDR | 9.2–21.7 pg/mL | ELISA | [122] | ||
Aqueous humor | DR | 4.04 ± 1.83 pg/mL * | Multiplex bead immunoassay | [115] | ||
Aqueous humor | PDR | 84.35 ± 30.82 pg/mL * | CBA technique | [123] | ||
Vitreous fluid | DR | 155.8 ± 82.0 pg/mL * | ELISA | [124] | ||
IFN-y | Tears | DR | 1957.50 ± 166.1 pg/mL * | Multiplex assay Bio-Plex system | [113] | |
VEGF-A | Aqueous humor | DR | 357.02 ± 84.25 pg/mL * | Multiplex bead immunoassay | [115] | |
VEGF | Tears | DR | 270.7 ± 40.2 pg/mL * | Multiplex assay Bio-Plex system | [113] | |
Aqueous humor | PDR | 211.62 pg/mL (48.10–1990.98) ** | Immunology Multiplex Assay | [83] | ||
Vitreous fluid | PDR progression | 1789.2 pg/mL (198.5–3436.8) ** | ELISA | [116] | ||
Vitreous | DR | 731.20 ± 222.72 pg/mL * | ELISA | [117] | ||
Vitreous | DR | 1491.0 ± 183.1 pg/mL * | ELISA | [125] | ||
EGF | Tears | DED | 1318.9 ± 6 835.0 pg/mL * | Milliplex bead assay | [126] | |
Apoptosis | MMP-9 | Tears | DED | 40 ng/mL | Immunoplex | [74,127] |
Aqueous | PDR | 160.3 ± 39.5 AU/mL * | Zymographic analysis | [128] | ||
Vitreous | Macular hole | 113.9 ± 229.7 AU/mL * | Zymographic analysis | [129] | ||
Cytochrome-C | Tears/Cell culture | DED | - | Cell culture | [130] |
MiRNA | Role | Matrix | Comparison | Result | Author(s) |
---|---|---|---|---|---|
miR-200b | Angiogenesis promotion [167] | Vitreous humor | PDR vs. NDM | Higher | Gomaa A, 2017 [168] |
miR-21 | Fibrosis and inflammation promotion [169] | Vitreous humor | PVD vs. MH | Higher | Usui-Ouchi A, 2016 [170] |
miR-15a | Angiogenesis inhibition [171] | Vitreous humor | PDR vs. MH | Higher | Hirota K, 2015 [172] |
Pro-inflammatory signaling inhibition [173] | Aqueous humor + | DME + | + Cho Heeyoon,2020 [174] | ||
miR-320 | Apoptosis regulation and angiogenesis repression [175] | Vitreous humor | PVD vs. MH | Higher | Usui-Ouchi A, 2016 [170] |
miR-320a miR 320b | Angiogenesis repression [176] | Vitreous humor | PDR vs. MH | Higher | Hirota K, 2015 [172] |
miR-184 | Apoptosis promotion [177] | Aqueous humor | PDR vs. Cataract | Higher | Chen S, 2019 [178] |
miR-93 miR-93-5p | Proliferation and angiogenesis promotion [179] | Vitreous humor | PDR vs. NDM | Higher | Hirota K, 2015 [172] |
Aqueous humor | PDR vs. Cataract | Chen S, 2019 [178] | |||
miR-29a | Angiogenesis inhibition [180] | Vitreous humor | PDR vs. MH | Higher | Hirota, K 2015 [172] |
Aqueous humor + | Cataract + | + Wecker T, 2016 [93] | |||
miR-16 miR-16-5p | Tumor suppression [181] | Vitreous humor | PVD vs. MH | Higher | Usui-Ouchi A, 2016 [170] |
Aqueous humor + | Cataract + | Wecker T, 2016 [93] | |||
miR-23a | Senescence promotion [182] | Vitreous humor | PDR vs. MH | Higher | Hirota K, 2015 [172] |
miR-126 | HMGB1 and VCAM-1 regulation [173] | Aqueous humor | PDR vs. Cataract | Lower | Chen S, 2019 [178] |
Let-7e | Proliferation inhibition [183] | Vitreous humor | PVD vs. MH | Lower | Usui-Ouchi A, 2016 [170] |
miR-204 | Apoptosis promotion [184] | Vitreous humor | PVD vs. macular hole | Lower | Usui-Ouchi A, 2016 [170] |
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López-Contreras, A.K.; Martínez-Ruiz, M.G.; Olvera-Montaño, C.; Robles-Rivera, R.R.; Arévalo-Simental, D.E.; Castellanos-González, J.A.; Hernández-Chávez, A.; Huerta-Olvera, S.G.; Cardona-Muñoz, E.G.; Rodríguez-Carrizalez, A.D. Importance of the Use of Oxidative Stress Biomarkers and Inflammatory Profile in Aqueous and Vitreous Humor in Diabetic Retinopathy. Antioxidants 2020, 9, 891. https://doi.org/10.3390/antiox9090891
López-Contreras AK, Martínez-Ruiz MG, Olvera-Montaño C, Robles-Rivera RR, Arévalo-Simental DE, Castellanos-González JA, Hernández-Chávez A, Huerta-Olvera SG, Cardona-Muñoz EG, Rodríguez-Carrizalez AD. Importance of the Use of Oxidative Stress Biomarkers and Inflammatory Profile in Aqueous and Vitreous Humor in Diabetic Retinopathy. Antioxidants. 2020; 9(9):891. https://doi.org/10.3390/antiox9090891
Chicago/Turabian StyleLópez-Contreras, Ana Karen, María Guadalupe Martínez-Ruiz, Cecilia Olvera-Montaño, Ricardo Raúl Robles-Rivera, Diana Esperanza Arévalo-Simental, José Alberto Castellanos-González, Abel Hernández-Chávez, Selene Guadalupe Huerta-Olvera, Ernesto German Cardona-Muñoz, and Adolfo Daniel Rodríguez-Carrizalez. 2020. "Importance of the Use of Oxidative Stress Biomarkers and Inflammatory Profile in Aqueous and Vitreous Humor in Diabetic Retinopathy" Antioxidants 9, no. 9: 891. https://doi.org/10.3390/antiox9090891
APA StyleLópez-Contreras, A. K., Martínez-Ruiz, M. G., Olvera-Montaño, C., Robles-Rivera, R. R., Arévalo-Simental, D. E., Castellanos-González, J. A., Hernández-Chávez, A., Huerta-Olvera, S. G., Cardona-Muñoz, E. G., & Rodríguez-Carrizalez, A. D. (2020). Importance of the Use of Oxidative Stress Biomarkers and Inflammatory Profile in Aqueous and Vitreous Humor in Diabetic Retinopathy. Antioxidants, 9(9), 891. https://doi.org/10.3390/antiox9090891