Effects of chondrocyte-derived extracellular matrix in a dry eye mouse model

Mol Vis. 2015 Oct 26:21:1210-23. eCollection 2015.

Abstract

Purpose: The occurrence of repetitive dry eye is accompanied by inflammation. This study investigated the anti-inflammatory effects of chondrocyte-derived extracellular matrix (CDECM) on the cornea and conjunctiva in a dry eye mouse model.

Methods: Dry eyes were experimentally induced in 12- to 16-week-old NOD.B10.H2(b) mice (Control) via subcutaneous injections of scopolamine (muscarinic receptor blocker) and exposure to an air draft for 10 days (desiccation stress [DS] 10D group). Tear volume and corneal smoothness were measured at 3, 5, 7, and 10 days after the instillation of PBS (PBS group) or CDECM (CDECM group). The corneas and conjunctivas were sectioned and stained with hematoxylin and eosin (H&E) and periodic acid Schiff (PAS). The expression of inflammatory markers (i.e., tumor necrosis factor-α [TNF-α], matrix metalloproteinase-2 [MMP-2], MMP-9, intercellular adhesion molecule-1 [ICAM-1], and vascular cell adhesion molecule-1 [VCAM-1]) was detected by quantitative real-time (qRT)-PCR and western blotting. All data were statistically processed using SPSS version 18.0.

Results: The instillation of CDECM after the removal of the DS increased tear production by up to 3.0-fold, and corneal smoothness improved to 80% compared to the PBS group (p<0.05). In the CDECM group, the detachment of the corneal epithelial cells was reduced by 73.3% compared to the PBS group, and the conjunctival goblet cell density was significantly recovered to the control levels (p<0.05). The expression of inflammatory factors was decreased in the cornea and conjunctiva of the CDECM group compared to the PBS group.

Conclusions: These observations suggest that CDECM induced effective anti-inflammatory improvements in the cornea and conjunctiva in this experimental model of dry eye.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Chondrocytes / chemistry*
  • Complex Mixtures / chemistry
  • Complex Mixtures / pharmacology*
  • Conjunctiva / drug effects
  • Conjunctiva / metabolism
  • Conjunctiva / pathology
  • Cornea / drug effects
  • Cornea / metabolism
  • Cornea / pathology
  • Desiccation
  • Disease Models, Animal
  • Extracellular Matrix / chemistry*
  • Gene Expression Regulation
  • Humans
  • Injections, Subcutaneous
  • Intercellular Adhesion Molecule-1 / genetics
  • Intercellular Adhesion Molecule-1 / metabolism
  • Male
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism
  • Mice
  • Mice, Inbred NOD
  • Ophthalmic Solutions
  • Scopolamine
  • Signal Transduction
  • Tears / drug effects*
  • Tears / metabolism
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism
  • Vascular Cell Adhesion Molecule-1 / genetics
  • Vascular Cell Adhesion Molecule-1 / metabolism
  • Xerophthalmia / chemically induced
  • Xerophthalmia / genetics
  • Xerophthalmia / metabolism
  • Xerophthalmia / pathology
  • Xerophthalmia / therapy*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Complex Mixtures
  • Icam1 protein, mouse
  • Ophthalmic Solutions
  • Tumor Necrosis Factor-alpha
  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1
  • Scopolamine
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9