Stanford Department of Chemical Engineering, Stanford, CA, USA.
Global Drug Development, Novartis Pharma, Basel, Switzerland.
Transl Vis Sci Technol. 2022 Sep 1;11(9):9. doi: 10.1167/tvst.11.9.9.
To investigate and quantify the effect of recombinant human lubricin (rh-lubricin) on model tear film stability.
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.
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.
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.
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.
研究和量化重组人润滑剂（rh-lubricin）对模型泪膜稳定性的影响。
使用一种称为界面去湿和排水光学平台的定制干涉测量仪器来创建和记录模型非细胞泪膜的时空演化。使用 MATLAB 进行图像分割和分析，从湿区分数随时间变化的曲线中提取最基本的特征，即蒸发破裂时间和最终湿区分数（A10）。这两个参数表示在 rh-lubricin 的无应力和应力形式下泪膜的稳定性。
我们的参数成功地捕捉到了随着 rh-lubricin 浓度的增加泪膜稳定性增加的趋势，并捕捉到了在各种工业相关应激后 rh-lubricin 功效的差异。具体而言，由 4 周高温应激引起的聚集和碎片化对 rh-lubricin维持模型泪膜稳定性的能力产生了负面影响。单独吸附的 rh-lubricin不足以抵抗破裂并保持模型泪膜表面的全覆盖。
我们的结果表明，碎片化和聚集会对 rh-lubricin 维持稳定泪膜的能力产生负面影响。此外，rh-lubricin 保持湿润面积覆盖的能力既归因于自由分散的 rh-lubricin，也归因于吸附的 rh-lubricin。
我们的平台和分析方法提供了一种简便、直观且与临床相关的方法，可用于量化眼科药物和制剂对改善泪膜稳定性的效果，并捕捉与药物稳定性和功效相关的变体之间的差异。
