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Association of tear proteins with Meibomian gland disease and dry eye symptoms
  1. Louis Tong1,2,3,
  2. Lei Zhou1,4,
  3. Roger W Beuerman1,2,4,
  4. Shao Zhen Zhao5,
  5. Xiao Rong Li5
  1. 1Singapore Eye Research Institute, Singapore, Singapore
  2. 2Singapore National Eye Centre, Singapore, Singapore
  3. 3Duke-NUS Graduate Medical School, Singapore, Singapore
  4. 4Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
  5. 5Tianjin Medical University Eye Center, Tianjin, China
  1. Correspondence to Professor Roger W Beuerman, Singapore Eye Research Institute, 11 Third Hospital Avenue, Singapore 168751; rwbeuer{at}


Aim Tear proteins have an important role in the maintenance of the ocular surface and modulation of biological processes, including inflammation, in dry eye. Meibomian gland disease (MGD) is a condition that can increase inflammation in the ocular surface, but tear protein changes due to MGD have not been documented. This study evaluated the possible association of tear proteins with severity of MGD in dry eye.

Methods Twenty-four patients with dry eye were evaluated. The panel of proteins found previously to be of interest and evaluated in this study were α-enolase, α-1-acid glycoprotein 1, S100A8 (calgranulin A), S100A9 (calgranulin B), S100A4 and S100A11 (calgizzarin), prolactin-inducible protein (PIP), lipocalin-1, lactoferrin and lysozyme. Tear protein ratios for each of 24 patients were calculated relative to pooled control from 18 healthy people, using isobaric tagging for relative and absolute quantification (iTRAQ)-based proteomics combined with two-dimensional-nanoliquid chromatography (LC)-nano-electrospray ionisation (ESI)-mass spectrometry (MS)/MS. The severity of MGD was clinically classified into grades 0–3 based on biomicroscopic signs.

Results The levels of S100A8 and S100A9 were correlated to MGD severity. The level of S100A8 protein was significantly correlated to grittiness, whereas S100A8 and S100A9 were correlated to symptoms of redness and transient blurring. Lipocalin-1 was associated with heaviness of the eyelids and tearing.

Conclusions Distinct tear proteins are associated with MGD in dry eye patients, and some proteins were associated with distinct dry eye symptoms. These findings suggest that MGD may independently contribute to the symptomatology of dry eye patients.

  • Dry eye
  • biomarker
  • tear proteomics
  • iTRAQ
  • quantitative proteomics
  • Meibomian gland disease
  • eye lids
  • tears
  • lacrimal gland
  • ocular surface

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  • Funding Grants NMRC/0808/2003, NMRC/CPG/002/2003, NMRC/0982/2005 and NMRC/1206/2009 from National Medical Research Council (NMRC), Singapore; an unrestricted grant from Allergan (Irvine, California, USA); and grant 07JCYBJ09800 from Tianjin Committee of Science and Technology Fundamental Research Project.

  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval This study was conducted with the approval of the Institutional Review Board of the Singapore Eye Research Institute and Tianjin Medical University Eye Center.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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