A highly soluble matrix metalloproteinase-9 inhibitor for potential treatment of dry eye syndrome

Basic Clin Pharmacol Toxicol. 2012 Nov;111(5):289-95. doi: 10.1111/j.1742-7843.2012.00896.x. Epub 2012 May 18.

Abstract

Dry eye syndrome (DES) or keratoconjunctivitis sicca is an eye disease caused by the chronic lack of lubrication and moisture of the eye. The pathogenesis of DES involves the over-expression and over-activity of corneal Matrix Metalloproteinase 9 (MMP-9). We propose herein a new, non-symptomatic approach for the treatment of DES based on the inhibition of MMP-9 by a new highly soluble molecule, designed as PES_103 that has been shown to inhibit MMP-9 both in vitro and in vivo. The efficacy of PES_103 in vivo and the potential benefits of this treatment in restoring tear production were studied in this work using an animal model of reduced lacrimation. PES_103 did not show any significant corneal toxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cornea / drug effects*
  • Cornea / enzymology
  • Cornea / metabolism
  • Cornea / pathology
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Dry Eye Syndromes / drug therapy*
  • Dry Eye Syndromes / enzymology
  • Dry Eye Syndromes / metabolism
  • Dry Eye Syndromes / pathology
  • Female
  • Humans
  • Hydroxamic Acids / adverse effects
  • Hydroxamic Acids / chemistry
  • Hydroxamic Acids / pharmacology
  • Hydroxamic Acids / therapeutic use*
  • Keratoconjunctivitis Sicca / drug therapy
  • Keratoconjunctivitis Sicca / enzymology
  • Keratoconjunctivitis Sicca / metabolism
  • Keratoconjunctivitis Sicca / pathology
  • Matrix Metalloproteinase 2 / chemistry
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / chemistry*
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism
  • Matrix Metalloproteinase Inhibitors / adverse effects
  • Matrix Metalloproteinase Inhibitors / chemistry
  • Matrix Metalloproteinase Inhibitors / pharmacology
  • Matrix Metalloproteinase Inhibitors / therapeutic use*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Molecular Targeted Therapy*
  • Ophthalmic Solutions
  • Recombinant Proteins / antagonists & inhibitors
  • Recombinant Proteins / metabolism
  • Solubility
  • Sulfonamides / adverse effects
  • Sulfonamides / chemistry
  • Sulfonamides / pharmacology
  • Sulfonamides / therapeutic use*
  • Tears / enzymology

Substances

  • 2-((2,3-dihydroxypropyl)((4-methoxyphenyl)sulfonyl)amino)-N-hydroxyacetamide
  • Hydroxamic Acids
  • Matrix Metalloproteinase Inhibitors
  • Ophthalmic Solutions
  • Recombinant Proteins
  • Sulfonamides
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9