The effect of sodium hyaluronate on the expression of gelatinases in rabbit corneal epithelial wound healing

Jpn J Ophthalmol. Sep-Oct 2000;44(5):475-81. doi: 10.1016/s0021-5155(00)00208-2.


Purpose: We investigated the effect of sodium hyaluronate (Na-HA) on the expression of gelatinases in a rabbit model with corneal epithelial defects.

Methods: Topical administration of Na-HA or phosphate-buffered saline (PBS) was carried out in the experimental eyes after surgical removal of the corneal epithelium. At 0, 6, 24, 48, and 72 hours after wounding, mRNA expression of 72 kDa type gelatinase (MMP-2), 92 kDa type gelatinase (MMP-9), and tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) were analyzed by reverse transcription polymerase chain reaction in those corneas. In addition, gelatinolytic activities were investigated using gelatin zymography.

Results: The levels of constitutive expression of MMP-2 and TIMP-1 mRNA persisted, whereas MMP-9 mRNA in the PBS-treated side was expressed temporarily after surgical removal. In the Na-HA-treated side, at 6 hours after wounding, a much higher expression of MMP-9 mRNA was reproducibly observed compared with that in the PBS-treated side. In zymography, the levels of gelatinolytic activity corresponding to proMMP-9 were significantly higher in the Na-HA-treated side than in the PBS-treated side at 6 hours after wounding.

Conclusions: These results suggest a novel participation of Na-HA in the expression of MMP-9 in rabbit corneal epithelial wound healing.

Publication types

  • Comparative Study

MeSH terms

  • Adjuvants, Immunologic / pharmacology*
  • Animals
  • Epithelium, Corneal / drug effects
  • Epithelium, Corneal / enzymology*
  • Epithelium, Corneal / injuries
  • Epithelium, Corneal / pathology
  • Eye Injuries / drug therapy
  • Eye Injuries / enzymology*
  • Eye Injuries / pathology
  • Female
  • Hyaluronic Acid / pharmacology*
  • Matrix Metalloproteinase 2 / biosynthesis
  • Matrix Metalloproteinase 2 / genetics*
  • Matrix Metalloproteinase 9 / biosynthesis
  • Matrix Metalloproteinase 9 / genetics*
  • Ophthalmic Solutions
  • Organ Culture Techniques
  • RNA, Messenger / biosynthesis*
  • Rabbits
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tissue Inhibitor of Metalloproteinase-1 / biosynthesis
  • Tissue Inhibitor of Metalloproteinase-1 / genetics*
  • Wound Healing / drug effects*


  • Adjuvants, Immunologic
  • Ophthalmic Solutions
  • RNA, Messenger
  • Tissue Inhibitor of Metalloproteinase-1
  • Hyaluronic Acid
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9