Table 3

Biomarker	Omics	Analytical Method	Sample Source	Marker type	Regulation (ratio)	Ref
Lipophilin Cystatin/lysozyme Lipophilin CL Lipocalin Unidentified β-2 Microglobulin Heterodimer of lipophilins A and C Apolipoprotein D monomer	Proteomics	1-D SDS-PAGE MALDI-TOF/MS ESI-QhQ/MS	Tear (Rabbit)	Surgically induced dry eye	Up (2.1) Up (2.8) Up (1.4) Up (1.1) Up (1.3) Down (0.4) Down (0.5) Down (0.7)	[59]
Lactoferrin EGF AQP5	Proteomics	ELISA	Tear (Human)	Dry eye (non-Sjögren, Sjögren & Stevens-Johnson Syndrome)	Down (0.06–0.34) Down (0.06–0.45) Up (4.0; Sjögren only)	[9]
α-1-antitrypsin, C-terminal fragment Calgranulin A Unidentified Nasopharyngeal carcinoma-associated proline-rich protein Proline-rich protein 4 Proline-rich protein 3 Unidentified	Proteomics	SELDI-TOF-MS (Shirmer tear collection)	Tear (Human)	Dry eye	Up (1.8) Up (3.0) Up (13.9) Down (0.37) Down (0.32) Down (0.40) Down (0.39)	[10]
Ten proteins (m/z data only)	Proteomic	SELDI-TOF-MS (Shirmer tear collection)	Tear (Human)	Sjögren syndrome	3-Up 7-Down	[7]
α-enolase α-1-acid glycoprotein 1 S100 A8 Calgranulin A S100 A9 Calgranulin B S100 A11 Calgizzarin S100 A4 Calcium-Binding protein Prolactin-inducible protein Lipocalin-1 Lactoferrin Lysozyme C	Proteomic	iTRAQ ESI-MS/MS	Tear (Human)	Dry eye	Up (1.7) Up (2.4) Up (1.4) Up (1.4) Up (1.7) Up (2.3) Down (0.59) Down (0.76) Down (0.79) Down (0.70)	[44]
Metalloproteinase-9	Proteomic	ELISA	Tear (Human)	Dry eye	Up (4.2–45.4)	[60]
EGF Fractalkine/CX3CL1 IL-1Ra IP-10/CXCL10 VEGF	Proteomic	Multiplex bead analysis	Tear (Human)	Dry eye	Up (>10) Up (>10) Up (10) Up (10) Up (<10)	[17]
Proline-rich 4 protein	Proteomic	2-D electrophoretic analysis	Tear (Human)	Dry eye	Down (ND)	[46]

Ratio: (diseased eye)/(normal eye) ND: not determined, 1-D-SDS-PAGE: one-dimensional-sodium dodecyl sulfate polyacrylamide gel electrophoresis, MALDI-TOF/MS: matrix assisted laser desorption ionization-time of flight/mass spectrometry, SELDI-TOF: surface-enhanced laser desorption ionization-time of flight, ESI-QhQ: electrospray ionization-Quadrupolehexapole- quadrupole, ELISA: enzyme-linked immunosorbent assay, iTRAQ: isobaric tag for relative and absolute quantitation

Table 3: Tear- and meibum-associated potential protein biomarkers tentatively identified for dry eye syndrome in animal models and human subpopulations [28].