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Michael L. Samsom, Benjamin D. Sullivan, Tannin A. Schmidt; Effect of Hyperosmolarity on PRG4’s Ocular Surface Boundary Lubricating Ability at a Human Cornea-Eyelid Biointerface. Invest. Ophthalmol. Vis. Sci. 2012;53(14):551.
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© ARVO (1962-2015); The Authors (2016-present)
Recent studies indicate that the mucin-like boundary lubricant proteoglycan 4 (PRG4) is expressed at the epithelium of the ocular surface and reduces friction during an eyelid blink or with contact lens wear. Both proteoglycans and mucins within the tear film are glycosylated structures with a strongly negative fixed charge density. As such, the lubrication properties of the ocular surface may be compromised by a hyperosmolar tear film, as observed in dry eye disease. The objective of this study was therefore to determine the effect of hyperosmolarity on PRG4’s ocular surface boundary lubricating ability at a human cornea-eyelid biointerface.
Fresh human corneas and eyelids were obtained from the Southern Alberta Organ & Tissue Donation Program - Lions Eye Bank, and the University of Calgary Body Donation Program, respectively. Tissues were mounted on a BOSE ELF3200 biomechanical testing machine with custom sample holders, forming a cornea-eyelid biointerface. Tissue surfaces were articulated against each other at effective sliding velocities ranging from 0.3-30 mm/s under physiological loads of 8-25 kPa. Samples (n=4) were first conditioned by testing in lubricant bath of SterilePlus saline (Baush & Lomb), followed by sequential testing in PRG4@300µg/mL in saline (SalPRG4), PRG4@300µg/mL in saline adjusted to 900 mOsm/L with NaCl (HyperSalPRG4), and then repeated in saline (Sal). Both static and kinetic friction coefficients were calculated.
PRG4 functioned as an extremely effective friction lowering ocular surface boundary lubricant at the cornea-eyelid biointerface when resuspend in isotonic saline, but not when it was resuspended in a hyperosmolar saline. At all sliding velocities, kinetic friction coefficients were relatively invariant with sliding velocity, and were lowest in SalPRG4 (0.18±0.02 to 0.19±0.02, mean±SEM), highest in HyperSalPRG4 (0.35±005. to 0.41±0.05), and intermediate but still elevated in saline (0.27±0.02 to 0.32±0.02). Static friction coefficients increased with velocity, and similar trends were observed between test lubricants.
These data support the hypothesis that PRG4 protects the ocular surface against friction, while hyperosmolar solutions result in increased friction on the ocular surface during an eyelid blink or contact lens wear. As such, therapeutic interventions of dry eye disease should seek to maintain a healthy tear film osmolarity in order to minimize the friction at the cornea-lid interface.
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