Effect of Recombinant Human Lubricin on Model Tear Film Stability

重组人润滑蛋白对模型泪膜稳定性的影响

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Abstract

PURPOSE: To investigate and quantify the effect of recombinant human lubricin (rh-lubricin) on model tear film stability. METHODS: A custom-built, interferometry-based instrument called the Interfacial Dewetting and Drainage Optical Platform was used to create and record the spatiotemporal evolution of model acellular tear films. Image segmentation and analysis was performed in MATLAB to extract the most essential features from the wet area fraction versus time curve, namely the evaporative break-up time and the final wet area fraction (A10). These two parameters indicate the tear film stability in the presence of rh-lubricin in its unstressed and stressed forms. RESULTS: Our parameters successfully captured the trend of increasing tear film stability with increasing rh-lubricin concentration, and captured differences in rh-lubricin efficacy after various industrially relevant stresses. Specifically, aggregation and fragmentation caused by a 4-week, high temperature stress condition negatively impacted rh-lubricin's ability to maintain model tear film stability. Adsorbed rh-lubricin alone was not sufficient to resist break-up and maintain full area coverage of the model tear film surface. CONCLUSIONS: Our results demonstrate that fragmentation and aggregation can negatively impact rh-lubricin's ability to maintain a stable tear film. In addition, the ability of rh-lubricin to maintain wetted area coverage is due to both freely dispersed and adsorbed rh-lubricin. TRANSLATIONAL RELEVANCE: Our platform and analysis method provide a facile, intuitive, and clinically relevant means to quantify the effect of ophthalmic drugs and formulations intended for improving tear film stability, as well as capture differences between variants related to drug stability and efficacy.

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