Rau Anna-Lena, Schicht Martin, Zahn Ingrid, Ali Mohammad Javed, Coroneo Minas Theodore, Paulsen Friedrich
Functional and Clinical Anatomy, Friedrich Alexander University, Erlangen, Germany.
Functional and Clinical Anatomy, Friedrich Alexander University, Erlangen, Germany.
Ocul Surf. 2024 Oct;34:296-308. doi: 10.1016/j.jtos.2024.08.016. Epub 2024 Aug 31.
Our aim was to evaluate a potential role for the lacrimal drainage system (LDS) as a portal of entry and conduit for SARS-CoV-2 in human infection. We also investigate the mucosal surface area. The relatively long tear contact time in a closed system raises the possibility that this pathway may contribute to the initiation of systemic infection. We looked for expression of ACE2, the main receptor for SARS-CoV-2, as well as cofactors such as TMPRSS2 and other enzymes such as cathepsinB, CD147, elastase1, furin, neuropilin1, neuropilin2, TMPRSS11D and trypsin which also play a role in SARS-CoV-2 infection, in this system.
Human tissue samples of the draining tear ducts from body donors were analyzed by RT-PCR, Western blot and immunohistochemistry. It is not known whether the respective body donors were Sars-Cov-2 positive at any time; they were negative when they entered the institute. Besides, the draining LDS of body donors were measured to determine the mucosal surface in the lacrimal system.
The expression of the main receptor studied, ACE2, cofactors such as TMPRSS2 and other enzymes such as cathepsinB, CD147, elastase1, furin, neuropilin1, neuropilin2, TMPRSS11D and trypsin were all detected at the gene and protein level. The average mucosal surface area of the lacrimal sac and nasolacrimal duct was calculated to be 110 mm.
The results show the presence of all analyzed receptors in the efferent LDS. With an average tear passage time of 3 min and a relatively large mucosal surface area, the LDS could therefore be considered as a portal of entry and conduit for SARS-CoV-2. In addition, it represents a surface that should be taken into consideration in the administration of topically applied medication to the ocular surface.
我们的目的是评估泪道系统(LDS)作为严重急性呼吸综合征冠状病毒2(SARS-CoV-2)进入人体的门户和传播途径的潜在作用。我们还研究了黏膜表面积。在封闭系统中相对较长的泪液接触时间增加了这种途径可能导致全身感染的可能性。我们在该系统中寻找SARS-CoV-2的主要受体血管紧张素转换酶2(ACE2)以及诸如跨膜丝氨酸蛋白酶2(TMPRSS2)等辅助因子和诸如组织蛋白酶B、CD147、弹性蛋白酶1、弗林蛋白酶、神经纤毛蛋白1、神经纤毛蛋白2、TMPRSS11D和胰蛋白酶等在SARS-CoV-2感染中也起作用的其他酶的表达。
通过逆转录聚合酶链反应(RT-PCR)、蛋白质免疫印迹法和免疫组织化学法对尸体捐献者引流泪道的人体组织样本进行分析。尚不清楚各尸体捐献者在任何时候是否为SARS-CoV-2阳性;他们进入研究所时为阴性。此外,测量尸体捐献者的引流泪道系统以确定泪道系统中的黏膜表面积。
在所研究的主要受体ACE2、辅助因子TMPRSS2以及组织蛋白酶B、CD147、弹性蛋白酶1、弗林蛋白酶、神经纤毛蛋白1、神经纤毛蛋白2、TMPRSS11D和胰蛋白酶等其他酶均在基因和蛋白水平被检测到。泪囊和鼻泪管的平均黏膜表面积经计算为110平方毫米。
结果显示在所分析的传出泪道系统中存在所有受体。鉴于泪液平均通过时间为3分钟且黏膜表面积相对较大,泪道系统因此可被视为SARS-CoV-2的进入门户和传播途径。此外,它代表了在向眼表局部应用药物时应予以考虑的一个表面。