Abstract：
Cataracts are the world\'s number one blinding eye disease. Cataracts can only be effectively treated surgically, although there is a chance of surgical complications. One of the pathogenic processes of cataracts is oxidative stress, which closely correlated with pyroptosis. SIRT1 is essential for the regulation of pyroptosis. Nevertheless, the role of SIRT1 in formation of cataracts is unclear. In this work, we developed an in vitro model of shortwave blue light (SWBL)-induced scotomization in human lens epithelial cells (HLECs) and an in vivo model of SWBL-induced cataracts in rats. The study aimed to understand how the SIRT1/NF-κB/NLRP3 pathway functions. Additionally, the evaluation included cell death and the release of lactate dehydrogenase (LDH), a cytotoxicity marker, from injured cells. First, we discovered that SWBL exposure resulted in lens clouding in Sprague- Dawley (SD) rats and that the degree of clouding was positively linked to the duration of irradiation. Second, we discovered that SIRT1 exhibited antioxidant properties and was connected to the NF-κB/NLRP3 pathway. SWBL irradiation inhibited SIRT1 expression, exacerbated oxidative stress, and promoted nuclear translocation of NF-κB and the activation of the NLRP3 inflammasome, which caused LEC pyroptosis and ultimately led to cataract formation. Transient transfection to increase the expression of SIRT1 decreased the protein expression levels of NF-κB, NLRP3, caspase-1, and GSDMD, inhibited HLEC pyroptosis, and reduced the release of LDH, providing a potential method for cataract prevention and treatment.
摘要：
白内障是世界上头号致盲眼病。白内障只能通过手术有效治疗，虽然有手术并发症的机会。白内障的致病过程之一是氧化应激，与焦亡密切相关。SIRT1对于调节焦亡是必需的。然而，SIRT1在白内障形成中的作用尚不清楚.在这项工作中,我们建立了短波蓝光（SWBL）诱导的人晶状体上皮细胞（HLEC）切除的体外模型和SWBL诱导的大鼠白内障的体内模型。该研究旨在了解SIRT1/NF-κB/NLRP3通路的功能。此外,评估包括细胞死亡和乳酸脱氢酶（LDH）的释放，细胞毒性标记，受伤的细胞首先,我们发现SWBL暴露导致Sprague-Dawley（SD）大鼠晶状体混浊，混浊程度与照射时间呈正相关。第二,我们发现SIRT1表现出抗氧化特性,并与NF-κB/NLRP3通路相关.SWBL照射抑制SIRT1表达,加剧了氧化应激，并促进NF-κB的核转位和NLRP3炎性体的激活，这导致LEC焦亡并最终导致白内障形成。瞬时转染增加SIRT1的表达降低了NF-κB的蛋白表达水平,NLRP3，caspase-1和GSDMD，抑制HLEC焦凋亡，减少LDH的释放，为白内障的预防和治疗提供了一种潜在的方法。
