Meibomian Gland Dysfunction Is Associated with Low Levels of Immunoglobulin Chains and Cystatin-SN

Int J Mol Sci. 2023 Oct 12;24(20):15115. doi: 10.3390/ijms242015115.

Abstract

Meibomian gland dysfunction (MGD) is a highly prevalent condition and the most common cause of evaporative dry eye disease. Studying the proteome of MGD can result in important advances in the management of the condition. Here, we collected tear film samples from treatment naïve patients with MGD (n = 10) and age-matched controls (n = 11) with Schirmer filtration paper. The samples were analyzed with label-free quantification nano liquid chromatography-tandem mass spectrometry. The proteins were considered differentially expressed if p < 0.05. A total of 88 proteins were significantly regulated. The largest change was observed in cystatin-SN, which was downregulated in MGD and correlated negatively with tear meniscus height. The downregulation of cystatin-SN was confirmed with targeted mass spectrometry by single reaction monitoring (SRM). Eighteen immunoglobulin components involved in B cell activation, phagocytosis, and complement activation were downregulated in MGD including Ig alpha-1 chain C region, immunoglobulin J chain, immunoglobulin heavy variable 3-15, and Ig mu chain C region. The changes in cystatin-SN and immunoglobulin chains are likely to result from the inflammatory changes related to tear film evaporation, and future studies may assess their association with the meibum quality.

Keywords: blepharitis; cystatin; dry eye; immunoglobulin; mass spectrometry; meibomian gland dysfunction; proteome; proteomics; tear.

MeSH terms

  • Eyelid Diseases* / metabolism
  • Humans
  • Immunoglobulin Subunits / metabolism
  • Immunoglobulins / metabolism
  • Meibomian Gland Dysfunction* / metabolism
  • Meibomian Glands / metabolism
  • Salivary Cystatins / metabolism
  • Tears / metabolism

Substances

  • Immunoglobulin Subunits
  • Immunoglobulins
  • Salivary Cystatins
  • CST1 protein, human

Grants and funding

This research was generously funded by Fight for Sight Denmark and Synoptik-Fonden. The mass spectrometers applied for the study were kindly funded by A.P. Møller og Hustru Chastine Mc-Kinney Møllers Fond til almene Formaal.