Müller-Lierheim Wolfgang G K
CORONIS Foundation, 81241 Munich, Germany.
Diagnostics (Basel). 2020 Jul 23;10(8):511. doi: 10.3390/diagnostics10080511.
The chain length of hyaluronan (HA) determines its physical as well as its physiological properties. Results of clinical research on HA eye drops are not comparable without this parameter. In this article methods for the assessment of the average molecular weight of HA in eye drops and a terminology for molecular weight ranges are proposed. The classification of HA eye drops according to their zero shear viscosity and viscosity at 1000 s shear rate is presented. Based on the gradient of mucin MUC5AC concentration within the mucoaqueous layer of the tear film a hypothesis on the consequences of this gradient on the rheological properties of the tear film is provided. The mucoadhesive properties of HA and their dependence on chain length are explained. The ability of HA to bind to receptors on the ocular epithelial cells, and in particular the potential consequences of the interaction between HA and the receptor HARE, responsible for HA endocytosis by corneal epithelial cells is discussed. The physiological function of HA in the framework of ocular surface homeostasis and wound healing are outlined, and the influence of the chain length of HA on the clinical performance of HA eye drops is illustrated. The use of very high molecular weight HA (hylan A) eye drops as drug vehicle for the next generation of ophthalmic drugs with minimized side effects is proposed and its advantages elucidated. Consequences of the diagnosis and treatment of ocular surface disease are discussed.
透明质酸（HA）的链长决定了其物理和生理特性。若缺少该参数，关于HA滴眼液的临床研究结果便无法进行比较。本文提出了评估滴眼液中HA平均分子量的方法以及分子量范围的术语。介绍了根据HA滴眼液的零剪切粘度和1000 s剪切速率下的粘度进行的分类。基于泪膜粘蛋白层内粘蛋白MUC5AC浓度的梯度，提出了关于该梯度对泪膜流变学特性影响的假设。解释了HA的粘膜粘附特性及其对链长的依赖性。讨论了HA与眼上皮细胞上受体结合的能力，特别是HA与受体HARE之间相互作用的潜在后果，HARE负责角膜上皮细胞对HA的内吞作用。概述了HA在眼表稳态和伤口愈合框架中的生理功能，并说明了HA链长对HA滴眼液临床性能的影响。提出了使用超高分子量HA（hylan A）滴眼液作为下一代副作用最小的眼科药物的药物载体，并阐明了其优点。讨论了眼表疾病诊断和治疗的后果。
