Joint Shantou International Eye Center of Shantou University and the Chinese University of Hong Kong, Shantou, Guangdong, China; Shantou University Medical College, Shantou, Guangdong, China.
Joint Shantou International Eye Center of Shantou University and the Chinese University of Hong Kong, Shantou, Guangdong, China.
Exp Eye Res. 2022 Jan;214:108864. doi: 10.1016/j.exer.2021.108864. Epub 2021 Nov 24.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen for coronavirus disease 2019 (COVID-19) pandemic. Its infection depends on the binding of spike protein to the host cell receptor angiotensin-converting enzyme 2 (ACE2), type II transmembrane serine protease (TMPRSS2) and neuropilin-1 (NRP1). Hydroxychloroquine has been applied as one of the COVID-19 treatment strategies. Here we aimed to evaluate hydroxychloroquine treatment on SARS-CoV-2 receptor expression in human primary pterygium and conjunctival cells and its potential influences. Expression of ACE2, TMPRSS2 and NRP1 proteins were found in the epithelial layer of both primary pterygium and conjunctiva tissues as well as in their isolated fibroblasts. High concentration of hydroxychloroquine treatment significantly reduced the viability of both primary pterygium and conjunctival cells. ACE2 protein expression was significantly decreased in both pterygium and conjunctival cells after hydroxychloroquine treatment. Hydroxychloroquine also reduced NRP1 protein expression in conjunctival cells. In contrast, TMPRSS2 protein expression showed slightly increased in conjunctival cells. Notably, ROS production and SOD2 expression was significantly elevated in both pterygium and conjunctival cells after hydroxychloroquine treatment. In summary, this study revealed the reduction of ACE2 and NRP1 expression by hydroxychloroquine in human primary pterygium and conjunctival fibroblasts; yet with the increase in TMPRSS2 expression and oxidative stress and decrease in cell viability. Implementation of hydroxychloroquine for COVID-19 treatment should be carefully considered with its potential side effects and in combination with TMPRSS2 inhibitor.
严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）是 2019 年冠状病毒病（COVID-19）大流行的病原体。其感染依赖于刺突蛋白与宿主细胞受体血管紧张素转换酶 2（ACE2）、II 型跨膜丝氨酸蛋白酶（TMPRSS2）和神经纤毛蛋白-1（NRP1）的结合。羟氯喹已被应用于 COVID-19 治疗策略之一。在这里，我们旨在评估羟氯喹治疗对人原发性翼状胬肉和结膜细胞中 SARS-CoV-2 受体表达的影响及其潜在影响。在原发性翼状胬肉和结膜组织的上皮层以及其分离的成纤维细胞中均发现 ACE2、TMPRSS2 和 NRP1 蛋白的表达。高浓度的羟氯喹处理显著降低了原发性翼状胬肉和结膜细胞的活力。羟氯喹处理后，翼状胬肉和结膜细胞中的 ACE2 蛋白表达显著降低。羟氯喹还降低了结膜细胞中的 NRP1 蛋白表达。相比之下，TMPRSS2 蛋白表达在结膜细胞中略有增加。值得注意的是，羟氯喹处理后，在原发性翼状胬肉和结膜细胞中 ROS 产生和 SOD2 表达明显升高。综上所述，本研究揭示了羟氯喹在人原发性翼状胬肉和结膜成纤维细胞中降低 ACE2 和 NRP1 表达；然而，TMPRSS2 表达增加、氧化应激增加和细胞活力降低。在 COVID-19 治疗中实施羟氯喹应谨慎考虑其潜在的副作用，并与 TMPRSS2 抑制剂联合使用。
