Department of Pharmacology and Pharmaceutical Sciences (R.F., W.K., S.F.H.-A.), School of Pharmacy, Los Angeles, CA; and Department of Ophthalmology (R.F., W.K., M.H., M.C.E., S.F.H.-A.), Roski Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA.
Eye Contact Lens. 2020 Mar;46 Suppl 2(Suppl 2):S70-S83. doi: 10.1097/ICL.0000000000000641.
Tears are highly concentrated in proteins relative to other biofluids, and a notable fraction of tear proteins are proteases and protease inhibitors. These components are present in a delicate equilibrium that maintains ocular surface homeostasis in response to physiological and temporal cues. Dysregulation of the activity of protease and protease inhibitors in tears occurs in ocular surface diseases including dry eye and infection, and ocular surface conditions including wound healing after refractive surgery and contact lens (CL) wear. Measurement of these changes can provide general information regarding ocular surface health and, increasingly, has the potential to give specific clues regarding disease diagnosis and guidance for treatment. Here, we review three major categories of tear proteases (matrix metalloproteinases, cathepsins, and plasminogen activators [PAs]) and their endogenous inhibitors (tissue inhibitors of metalloproteinases, cystatins, and PA inhibitors), and the changes in these factors associated with dry eye, infection and allergy, refractive surgery, and CLs. We highlight suggestions for development of these and other protease/protease inhibitor biomarkers in this promising field.
眼泪中蛋白质的浓度相对其他生物体液更高，且泪液中的蛋白质有相当一部分是蛋白酶和蛋白酶抑制剂。这些成分处于微妙的平衡之中，能够响应生理和时间线索，维持眼表面的稳态。在包括干眼症和感染在内的眼表面疾病，以及包括屈光手术后和接触镜（CL）佩戴后的眼表面状况中，泪液中蛋白酶和蛋白酶抑制剂的活性会失调。这些变化的测量可以提供有关眼表面健康的一般信息，并且越来越有潜力为疾病诊断提供具体线索，并为治疗提供指导。在这里，我们回顾了三大类泪液蛋白酶（基质金属蛋白酶、组织蛋白酶和纤溶酶原激活物[PAs]）及其内源性抑制剂（金属蛋白酶组织抑制剂、半胱氨酸蛋白酶抑制剂和 PA 抑制剂），以及这些因素与干眼症、感染和过敏、屈光手术和 CL 相关的变化。我们强调了在这个充满希望的领域中开发这些和其他蛋白酶/蛋白酶抑制剂生物标志物的建议。
