School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland.
Head and Neck Center, Ophthalmology Research Unit, Helsinki University Central Hospital, Helsinki, Finland.
Int Ophthalmol. 2024 Mar 26;44(1):158. doi: 10.1007/s10792-024-03067-z.
Rhegmatogenous retinal detachment is a severe vision-threatening complication that can result into proliferative vitreoretinopathy (PVR) and re-detachment of the retina if recovery from surgery fails. Inflammation and changes in retinal pigment epithelial (RPE) cells are important contributors to the disease. Here, we studied the effects of simvastatin and amfenac on ARPE-19 cells under inflammatory conditions.
ARPE-19 cells were pre-treated with simvastatin and/or amfenac for 24 h after which interleukin (IL)-1α or IL-1β was added for another 24 h. After treatments, lactate dehydrogenase release, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) processing, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activity, prostaglandin E2 (PGE2) level, and extracellular levels of IL-6, IL-8, monocytic chemoattractant protein (MCP-1), vascular endothelial growth factor (VEGF), and pigment epithelium-derived factor, as well as the production of reactive oxygen species (ROS) were determined.
Pre-treatment of human ARPE-19 cells with simvastatin reduced the production of IL-6, IL-8, and MCP-1 cytokines, PGE2 levels, as well as NF-κB activity upon inflammation, whereas amfenac reduced IL-8 and MCP-1 release but increased ROS production. Together, simvastatin and amfenac reduced the release of IL-6, IL-8, and MCP-1 cytokines as well as NF-κB activity but increased the VEGF release upon inflammation in ARPE-19 cells.
Our present study supports the anti-inflammatory capacity of simvastatin as pre-treatment against inflammation in human RPE cells, and the addition of amfenac complements the effect. The early modulation of local conditions in the retina can prevent inflammation induced PVR formation and subsequent retinal re-detachment.
孔源性视网膜脱离是一种严重威胁视力的并发症,如果手术恢复失败,可能导致增生性玻璃体视网膜病变(PVR)和视网膜再次脱离。炎症和视网膜色素上皮(RPE)细胞的变化是疾病的重要诱因。在这里,我们研究了辛伐他汀和氨芬酸在炎症条件下对 ARPE-19 细胞的影响。
用辛伐他汀和/或氨芬酸预处理 ARPE-19 细胞 24 小时后,加入白细胞介素(IL)-1α或 IL-1β再处理 24 小时。处理后,测定乳酸脱氢酶释放、3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四唑溴盐(MTT)处理、核因子 kappa-轻链增强子的活性 B 细胞(NF-κB)、前列腺素 E2(PGE2)水平以及细胞外的白细胞介素-6(IL-6)、白细胞介素-8(IL-8)、单核细胞趋化蛋白-1(MCP-1)、血管内皮生长因子(VEGF)和色素上皮衍生因子,以及活性氧(ROS)的产生。
辛伐他汀预处理人 ARPE-19 细胞可减少炎症时细胞因子 IL-6、IL-8 和 MCP-1、PGE2 水平和 NF-κB 活性的产生,而氨芬酸则减少 IL-8 和 MCP-1 的释放,但增加 ROS 的产生。辛伐他汀和氨芬酸联合使用可减少炎症时 ARPE-19 细胞中 IL-6、IL-8 和 MCP-1 细胞因子以及 NF-κB 活性的释放,但增加 VEGF 的释放。
本研究支持辛伐他汀作为预处理对人 RPE 细胞炎症的抗炎作用,并补充了氨芬酸的作用。早期调节视网膜局部条件可以防止炎症诱导的 PVR 形成和随后的视网膜再脱离。