Department of Ophthalmology, Tufts University School of Medicine, at New England Eye Center, Tufts Medical Center, 800 Washington St, Boston, MA, 02111, USA.
USC Roski Eye Institute and Department of Ophthalmology, Keck School of Medicine of USC, University of Southern California, 1975 Zonal Ave, Los Angeles, CA, 90033, USA.
Prog Retin Eye Res. 2020 Mar;75:100777. doi: 10.1016/j.preteyeres.2019.100777. Epub 2019 Sep 4.
The mucosal glycocalyx of the ocular surface constitutes the point of interaction between the tear film and the apical epithelial cells. Membrane-associated mucins (MAMs) are the defining molecules of the glycocalyx in all mucosal epithelia. Long recognized for their biophysical properties of hydration, lubrication, anti-adhesion and repulsion, MAMs maintain the wet ocular surface, lubricate the blink, stabilize the tear film and create a physical barrier to the outside world. However, it is increasingly appreciated that MAMs also function as cell surface receptors that transduce information from the outside to the inside of the cell. A number of excellent review articles have provided perspective on the field as it has progressed since 1987, when molecular cloning of the first MAM was reported. The current article provides an update for the ocular surface, placing it into the broad context of findings made in other organ systems, and including new genes, new protein functions and new biological roles. We discuss the epithelial tissue-equivalent with mucosal differentiation, the key model system making these advances possible. In addition, we make the first systematic comparison of MAMs in human and mouse, establishing the basis for using knockout mice for investigations with the complexity of an in vivo system. Lastly, we discuss findings from human genetics/genomics, which are providing clues to new MAM roles previously unimagined. Taken together, this information allows us to generate hypotheses for the next stage of investigation to expand our knowledge of MAM function in intracellular signaling and roles unique to the ocular surface.
眼表面的黏膜糖萼构成了泪膜和顶端上皮细胞之间相互作用的点。膜相关粘蛋白 (MAMs) 是所有黏膜上皮糖萼的定义分子。MAMs 因其水合、润滑、抗黏附和排斥的生物物理特性而长期以来一直受到关注，它们维持着湿润的眼表面，润滑眨眼，稳定泪膜，并为外部世界创造物理屏障。然而，人们越来越认识到 MAMs 还作为细胞表面受体发挥作用，将外部信息传递到细胞内部。自 1987 年首次报道第一个 MAM 的分子克隆以来，许多优秀的综述文章为该领域提供了视角，该领域取得了进展。本文为眼表面提供了最新信息，将其置于在其他器官系统中发现的广泛背景下，并包括新基因、新蛋白质功能和新的生物学作用。我们讨论了具有黏膜分化的上皮组织等效物，这是取得这些进展的关键模型系统。此外，我们首次对人类和小鼠的 MAMs 进行了系统比较，为使用 knockout 小鼠在体内系统的复杂性下进行研究奠定了基础。最后，我们讨论了人类遗传学/基因组学的发现，这些发现为以前无法想象的 MAM 作用提供了线索。总之，这些信息使我们能够生成下一个研究阶段的假设，以扩大我们对 MAM 在细胞内信号转导中的作用以及眼表面特有的作用的认识。
