IRCCS Fodazione G. B. Bietti of Rome, Italy.
Curr Opin Allergy Clin Immunol. 2013 Oct;13(5):563-8. doi: 10.1097/ACI.0b013e3283645899.
Studies completed in the last decade provide new insights into the role of the epithelial glycocalyx in maintaining ocular surface barrier function. This review summarizes these findings, their relevance to allergic and infectious disease, and highlights the potential benefits of exploiting the modulation of barrier integrity for therapeutic gain.
The molecular components sealing the space between adjacent ocular surface epithelial cells, such as tight junctions, have been extensively characterized, and their contribution to the paracellular barrier established. A second layer of protection - the transcellular barrier - is provided by transmembrane mucins and their O-glycans on the glycocalyx. Cell surface glycans bind carbohydrate-binding proteins to promote formation of complexes that are no longer thought to be a static structure, but, instead, a dynamic system that responds to extrinsic signals and modulates pathogenic responses. Although functioning as a protective mechanism to maintain homeostasis, the glycocalyx also restricts drug targeting of epithelial cells.
The traditional model of intercellular junctions protecting the ocular surface epithelia has recently been expanded to include an additional glycan shield that lines apical membranes on the ocular surface. A better understanding of this apical barrier may lead to better management of ocular surface disease.
过去十年的研究为上皮细胞糖萼在维持眼表面屏障功能中的作用提供了新的见解。本综述总结了这些发现,及其与过敏和传染病的相关性,并强调了利用屏障完整性的调节来获得治疗效果的潜力。
已经广泛描述了封闭相邻眼表面上皮细胞之间空间的分子成分(如紧密连接),并确定了它们对细胞旁屏障的贡献。第二层保护 - 跨细胞屏障 - 由跨膜粘蛋白及其糖萼上的 O-聚糖提供。细胞表面聚糖结合糖结合蛋白,以促进复合物的形成,这些复合物不再被认为是静态结构,而是一个动态系统,它对外界信号做出反应,并调节致病反应。尽管糖萼作为一种保护机制来维持体内平衡,但它也限制了上皮细胞的药物靶向。
细胞间连接保护眼表面上皮细胞的传统模型最近已经扩展到包括另外一个糖萼,它排列在眼表面的顶膜上。对这个顶膜屏障的更好理解可能会导致更好地管理眼表面疾病。