Department of Chemical Engineering, Stanford University, Stanford, CA, 94305, USA.
Global Drug Development, Biopharmaceutical Process & Product Development, Novartis Pharma, Basel, AG 4002, Switzerland.
Adv Sci (Weinh). 2021 Aug;8(16):e2100841. doi: 10.1002/advs.202100841. Epub 2021 Jun 29.
Dry eye disease (DED) has high personal and societal costs, but its pathology remains elusive due to intertwined biophysical and biochemical processes at the ocular surface. Specifically, mucin deficiency is reported in a subset of DED patients, but its effects on ocular interfacial properties remain unclear. Herein a novel in vitro mucin-deficient mimetic ocular surface (Mu-DeMOS) with a controllable amount of membrane-tethered mucin molecules is developed to represent the diseased ocular surfaces. Contact angle goniometry on mimetic ocular surfaces reveals that high surface roughness, but not the presence of hydrophilic mucin molecules, delivers constant hydration over native ocular surface epithelia. Live-cell rheometry confirms that the presence of mucin-like glycoproteins on ocular epithelial cells reduces shear adhesive strength at cellular interfaces. Together, optimal surface roughness and surface chemistry facilitate sustainable lubrication for healthy ocular surfaces, while an imbalance between them contributes to lubrication-related dysfunction at diseased ocular epithelial surfaces. Furthermore, the restoration of low adhesive strength at Mu-DeMOS interfaces through a mucin-like glycoprotein, recombinant human lubricin, suggests that increased frictional damage at mucin-deficient cellular surfaces may be reversible. More broadly, these results demonstrate that Mu-DeMOS is a promising platform for drug screening assays and fundamental studies on ocular physiology.
干眼症（DED）给个人和社会带来了高昂的成本，但由于眼表面的生物物理和生化过程交织在一起，其病理学仍然难以捉摸。具体来说，据报道，一部分 DED 患者存在粘蛋白缺乏，但它对眼界面特性的影响尚不清楚。在此，开发了一种新型的具有可控数量的膜结合粘蛋白分子的体外粘蛋白缺乏模拟眼表面（Mu-DeMOS），以代表患病的眼表面。在模拟眼表面上进行接触角测角法表明，高表面粗糙度，而不是亲水性粘蛋白分子的存在，可提供比天然眼表上皮更恒定的水合作用。活细胞流变测量法证实，粘蛋白样糖蛋白存在于眼上皮细胞上可降低细胞界面处的剪切粘附强度。总的来说，最佳的表面粗糙度和表面化学性质有助于健康眼表面的可持续润滑，而它们之间的失衡则会导致患病眼上皮表面的润滑相关功能障碍。此外，通过粘蛋白样糖蛋白，重组人润滑剂，在 Mu-DeMOS 界面上恢复低粘附强度表明，粘蛋白缺陷细胞表面的摩擦损伤可能是可逆的。更广泛地说，这些结果表明 Mu-DeMOS 是药物筛选测定和眼生理基础研究的有前途的平台。
