Department of Ophthalmology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
Department of Orthopedics, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
Mol Med Rep. 2018 Aug;18(2):2277-2285. doi: 10.3892/mmr.2018.9188. Epub 2018 Jun 19.
An understanding of the mechanism of cataract formation may reduce its burden on medical care worldwide. It is established that pyroptosis is associated with oxidative stress, one of the causes of cataracts, and may provide novel therapeutic targets for the treatment of cataracts. The present study therefore investigated the role of pyroptosis in cataract formation. SRA01/04 human lens epithelium cells (HLECs) were treated with H2O2 and cell viability was assessed by an MTT assay. Pyroptosis in HLECs was examined by TUNEL staining, and the expression of caspase‑1 and interleukin (IL)‑1β was determined using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR), western blot analysis and immunostaining. A caspase‑1 inhibitor was used to investigate the effects of caspase‑1 downregulation. In addition, the expression of caspase‑1 and IL‑1β in lens anterior capsule tissue samples from patients with cataracts and normal controls was also analyzed by immunostaining, RT‑qPCR and western blot analysis. The results demonstrated that pyroptosis in H2O2‑treated HLECs, and the mRNA and protein expression of caspase‑1 and IL‑1β, was significantly increased compared with control cells. Furthermore, caspase‑1 and IL‑1β expression was significantly increased in cataract tissue samples compared with normal controls. When HLECs were cotreated with a caspase‑1 inhibitor and 100 µM H2O2, caspase‑1 and IL‑1β expression were decreased compared with the 100 µM H2O2‑only group. In conclusion, the results of the present study demonstrate that pyroptosis may have a role in cataract formation, and the caspase‑1 and IL‑1β pathways may be involved in this pathological process. Pyroptosis appears to be a promising target in the prevention of cataract formation.
对白内障形成机制的了解可能会降低其在全球医疗保健中的负担。已经确定细胞焦亡与氧化应激有关，氧化应激是白内障的原因之一，并且可能为白内障的治疗提供新的治疗靶点。因此，本研究探讨了细胞焦亡在白内障形成中的作用。用 H2O2 处理 SRA01/04 人晶状体上皮细胞（HLEC），并通过 MTT 测定法评估细胞活力。通过 TUNEL 染色检查 HLEC 中的细胞焦亡，并通过逆转录-定量聚合酶链反应（RT-qPCR）、western blot 分析和免疫染色测定半胱氨酸天冬氨酸蛋白酶-1（caspase-1）和白细胞介素（IL）-1β的表达。使用半胱氨酸天冬氨酸蛋白酶-1 抑制剂来研究 caspase-1 下调的影响。此外，还通过免疫染色、RT-qPCR 和 western blot 分析分析了白内障患者和正常对照者晶状体前囊组织样本中 caspase-1 和 IL-1β的表达。结果表明，与对照细胞相比，H2O2 处理的 HLEC 中的细胞焦亡以及 caspase-1 和 IL-1β 的 mRNA 和蛋白表达均显著增加。此外，与正常对照组相比，白内障组织样本中 caspase-1 和 IL-1β 的表达显著增加。当 HLEC 与半胱氨酸天冬氨酸蛋白酶-1 抑制剂和 100μM H2O2 共同处理时，与仅用 100μM H2O2 处理的组相比，caspase-1 和 IL-1β 的表达降低。综上所述，本研究的结果表明，细胞焦亡可能在白内障形成中起作用，并且 caspase-1 和 IL-1β 途径可能参与这一病理过程。细胞焦亡似乎是预防白内障形成的有希望的靶点。
