Tear-Derived Exosome Proteins Are Increased in Patients with Thyroid Eye Disease

Int J Mol Sci. 2021 Jan 23;22(3):1115. doi: 10.3390/ijms22031115.


Exosomes contain proteins, lipids, RNA, and DNA that mediate intercellular signaling. Exosomes can contribute to the pathological processes of various diseases, although their roles in ocular diseases are unclear. We aimed to isolate exosomes from tear fluids (TF) of patients with Thyroid eye disease (TED) and analyze the exosomal proteins. TFs were collected from eight patients with TED and eight control subjects. The number of TF exosomes were measured using nanoparticle-tracking analysis. The expression of specific proteins in the purified exosome pellets were analyzed using a Proteome Profiler Array Kit. Cultured normal orbital fibroblasts were incubated with TF exosomes from patients with TED and control subjects, and changes in inflammatory cytokine levels were compared. TF exosomes from TED patients showed more exosomes than the control subjects. The expression levels of exosomal proteins vitamin D-binding (VDB) protein, C-reactive protein (CRP), chitinase 3-like 1 (CHI3L1), matrix metalloproteinase-9 (MMP-9), and vascular adhesion molecule-1 (VCAM-1) were significantly increased in patients with TED, compared to those of controls. Orbital fibroblasts exposed to TF exosomes from patients with TED showed significantly higher levels of interleukin (IL)-6, IL-8, and monocyte chemoattractant protein-1 (MCP-1) production than those treated with control TF exosomes. Specific proteins showed higher expression in exosomes from TED patients, implying that they may play keys roles in TED pathogenesis.

Keywords: Graves’ ophthalmopathy; eear fluids; ehyroid-associated ophthalmopathy; exosomes; extracellular vesicle; eytokines.

MeSH terms

  • Adult
  • Aged
  • Case-Control Studies
  • Chitinase-3-Like Protein 1 / analysis
  • Chitinase-3-Like Protein 1 / metabolism
  • Cytokines / analysis
  • Cytokines / metabolism
  • Exosomes / chemistry*
  • Exosomes / pathology
  • Eye Proteins / analysis
  • Eye Proteins / metabolism*
  • Female
  • Fibroblasts / metabolism
  • Graves Ophthalmopathy / drug therapy
  • Graves Ophthalmopathy / pathology*
  • Humans
  • Male
  • Matrix Metalloproteinase 9 / analysis
  • Matrix Metalloproteinase 9 / metabolism
  • Methimazole / therapeutic use
  • Middle Aged
  • Tears / cytology*
  • Tears / metabolism
  • Vascular Cell Adhesion Molecule-1 / analysis
  • Vascular Cell Adhesion Molecule-1 / metabolism
  • Vitamin D-Binding Protein / analysis
  • Vitamin D-Binding Protein / metabolism


  • CHI3L1 protein, human
  • Chitinase-3-Like Protein 1
  • Cytokines
  • Eye Proteins
  • Vascular Cell Adhesion Molecule-1
  • Vitamin D-Binding Protein
  • tear proteins
  • Methimazole
  • MMP9 protein, human
  • Matrix Metalloproteinase 9