title: Dose-dependent and synergistic effects of proteoglycan 4 on boundary lubrication at a human cornea-polydimethylsiloxane biointerface.
abstract: OBJECTIVE
  Proteoglycan 4 (PRG4), also known as lubricin, is a boundary lubricating mucin-like glycoprotein present on several tissue surfaces in the body. The objectives of this study were to (1) implement and characterize an in vitro boundary lubrication test at a human cornea-polydimethylsiloxane (PDMS) biointerface and (2) determine the dose-dependent and synergistic effects of PRG4, with hyaluronan (HA), on ocular surface boundary lubrication using this test.
  
  
  METHODS
  Human corneas and model PDMS material were articulated against each other, at effective sliding velocities v(eff) between 0.3 and 30 mm/sec under physiologic loads of approximately 8 to 25 kPa. Samples were tested serially in (1) saline, PRG4 at 30, 100, 300 μg/mL resuspended in saline, then saline again or (2) saline, AQuify Comfort Eye Drops (containing 0.1% HA), 300 μg/mL PRG4 in saline, 300 μg/mL PRG4 in AQuify, then saline again. Both static and kinetic friction coefficients were calculated.
  
  
  RESULTS
  PRG4 effectively lowered friction at the cornea-PDMS biointerface, both alone in a dose-dependent manner and in combination with HA. PRG4 reduced kinetic friction coefficients, <μ(kinetic, Neq)>, from approximately 0.30 in saline, to approximately 0.30, 0.24, and 0.17 in 30, 100, and 300 μg/mL PRG4, respectively. Values of <μ(kinetic, Neq)> in AQuify, approximately 0.32, were similar to those in saline; however, when combined with 300 μg/mL PRG4, values of <μ(kinetic, Neq)> were reduced to approximately 0.15.
  
  
  CONCLUSIONS
  PRG4 functions as an effective ocular surface boundary lubricant, both alone in a dose-dependent manner and in combination with HA.
authors.affiliation: Faculty of Kinesiology, Human Performance Laboratory, University of Calgary, Calgary, Canada.
authors.forename: Sheila
authors.initials: S
authors.lastname: Morrison
authors.forename: David A
authors.initials: DA
authors.lastname: Sullivan
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Sullivan
authors.forename: Heather
authors.initials: H
authors.lastname: Sheardown
authors.forename: Tannin A
authors.initials: TA
authors.lastname: Schmidt
mesh_terms: D001672:Biocompatible Materials / Q000737:chemistry*; D003315:Cornea / Q000187:drug effects* / Q000502:physiology; D004129:Dimethylpolysiloxanes / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006801:Humans; D006820:Hyaluronic Acid / Q000494:pharmacology; D008153:Lubrication; D011509:Proteoglycans / Q000494:pharmacology*; D013312:Stress, Physiological / Q000502:physiology; D013499:Surface Properties; D000099158:Proteoglycan 4
chemical_list: D001672:Biocompatible Materials; D004129:Dimethylpolysiloxanes; D006820:Hyaluronic Acid; D011509:Proteoglycans; C419197:PRG4 protein, human; D000099158:Proteoglycan 4