PDF(Pubmed)
Abstract：
Age-related cataract (ARC) is the predominant cause of global blindness, linked to the progressive aging of the lens, oxidative stress, perturbed calcium homeostasis, hydration irregularities, and modifications in crystallin proteins. Currently, surgical intervention remains the sole efficacious remedy, albeit carrying inherent risks of complications that may culminate in irreversible blindness. It is urgent to explore alternative, cost-effective, and uncomplicated treatment modalities for cataracts. Lanosterol has been widely reported to reverse cataracts, but the mechanism of action is not yet clear. In this study, we elucidated the mechanism through which lanosterol operates in the context of cataract reversal. Through the targeted suppression of sterol regulatory element-binding protein 2 (SREBP2) followed by lanosterol treatment, we observed the restoration of lipid metabolism disorders induced by SREBP2 knockdown in lens epithelial cells (LECs). Notably, lanosterol exhibited the ability to effectively counteract amyloid accumulation and cellular apoptosis triggered by lipid metabolism disorders. In summary, our findings suggest that lanosterol, a pivotal intermediate in lipid metabolism, may exert its therapeutic effects on cataracts by influencing lipid metabolism. This study shed light on the treatment and pharmaceutical development targeting Age-related Cataracts (ARC).
摘要：
年龄相关性白内障（ARC）是全球失明的主要原因，与镜片的逐渐老化有关，氧化应激，扰乱钙稳态，水合不规则，和晶状体蛋白的修饰。目前,手术干预仍然是唯一有效的补救措施，尽管有固有的并发症风险，最终可能导致不可逆转的失明。迫切需要探索替代方案，成本效益高,和简单的白内障治疗方式。羊毛甾醇已被广泛报道可以逆转白内障，但作用机制尚不清楚。在这项研究中,我们阐明了羊毛甾醇在白内障逆转中的作用机制。通过靶向抑制甾醇调节元件结合蛋白2（SREBP2），然后进行羊毛甾醇治疗，我们观察到晶状体上皮细胞（LECs）中SREBP2敲低诱导的脂质代谢紊乱的恢复。值得注意的是,羊毛甾醇表现出有效抵抗脂质代谢紊乱引发的淀粉样蛋白积累和细胞凋亡的能力。总之,我们的研究结果表明羊毛甾醇，脂质代谢的关键中间体，可能通过影响脂质代谢来发挥其对白内障的治疗作用。这项研究揭示了针对年龄相关性白内障（ARC）的治疗和药物开发。
