Dose-Dependent and Synergistic Effects of Proteoglycan 4 on Boundary Lubrication at a Human Cornea-Polydimethylsiloxane Biointerface

Objectives: 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 nu(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 mu g/mL resuspended in saline, then saline again or (2) saline, AQuify Comfort Eye Drops (containing 0.1% HA), 300 mu g/mL PRG4 in saline, 300 mu g/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, , from approximately 0.30 in saline, to approximately 0.30, 0.24, and 0.17 in 30, 100, and 300 mu g/mL PRG4, respectively. Values of in AQuify, approximately 0.32, were similar to those in saline; however, when combined with 300 mu g/mL PRG4, values of 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.