Table 1.
Biomarker levels in tear, aqueous, and vitreous humor. Levels of the markers of oxidative stress, inflammation, and apoptosis measured in tear, aqueous, and vitreous humor in different ocular conditions, in addition to PDR, differentiating the different methodologies used. PDR: proliferative diabetic retinopathy, DED: dry eye disease, TAC: total antioxidant capacity, LPO: lipoperoxides, MDA: malondialdehyde, GSH: glutathione, GPx: glutathione peroxidase, SOD: superoxide dismutase, 8-OHdG: 8-hidroxi-2-deoxiguanosine, 8-IPGF: 8-isoprostaglandins, NO: nitric oxide, IL-6: interleukin-6, IL-8: interleukin-8, IL-10: interleukin-10, TNF-α: Tumour necrosis factor alpha, VEGF: vascular endothelial growth factor, EGF: epidermal grow factor, MMP-9: metalloproteinase-9, FN-kβ: Nuclear factor kβ, T1DM: type 1 diabetes mellitus, T2DM: type 2 diabetes mellitus.
| 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] |
* Data are expressed as the mean ± SD. ** Median values and 5th and 95th percentile values in pg/mL.