Objective: To explore the relationship between expression of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome and improvement of macular structure in patients with wet age-related macular degeneration (wAMD) after anti-vascular endothelial growth factor (VEGF) therapy. Methods: A before-after study was carried out. A total of 110 patients (110 eyes) with wAMD who were admitted to Department of Ophthalmology, People's Hospital Affiliated to Shandong First Medical University between August 2019 and December 2021 were enrolled, and all patients were given vitreous injection of anti-VEGF drug (ranibizumab or bevacizumab). The aqueous humor was collected to detect mRNA levels of NLRP3, cysteinyl aspartate specific protease-1 (Caspase-1), apoptosis-associated speck-like protein (ASC) and interleukin (IL) 1β by fluorescence quantitative PCR. The levels of IL-1β, IL-18, tumor necrosis factor α (TNF-α) and VEGF in aqueous humor were detected by enzyme-linked immunosorbent assay (ELISA). The correlation between the above indexes and central macular thickness (CMT) in wAMD patients was analyzed by multivariate linear regression analysis. Results: In the 110 wAMD patients, there were 68 males and 42 females, with a mean age of (68.7±7.6) years. Compared with those before treatment, mRNA levels of NLRP3 (1.65±0.27, 1.34±0.19 vs 1.97±0.23, both P<0.017), Caspase-1 (1.47±0.15, 1.29±0.17 vs 1.53±0.18, both P<0.017), ASC (1.33±0.14, 1.21±0.18 vs 1.47±0.12, both P<0.017) and IL-1β (1.78±0.21, 1.46±0.17 vs 2.21±0.24, both P<0.017), and levels of IL-1β [(26.9±5.7), (20.3±4.6) vs (33.6±8.3) ng/L, both P<0.017], IL-18 [(32.7±7.6), (23.3±6.9) vs (46.4±9.4) ng/L, both P<0.017], TNF-α [(39.4±6.6), (21.7±6.3) vs (52.9±9.1) ng/L, both P<0.017] and VEGF [(35.7±10.2), (23.4±6.7) vs (65.4±19.3) ng/L, both P<0.017] were decreased after the first and second injection. Moreover, the above-mentioned indexes after second injection were lower than those after the first injection (all P<0.017). The results of multivariate linear regression analysis showed that NLRP3 mRNA (the first injection: β=53.750, P<0.001; the second injection: β=94.648, P<0.001), IL-1β (the first injection: β=1.356, P=0.021; the second injection: β=2.008, P=0.003), IL-18 (the first injection: β=1.984, P<0.001; the second injection: β=1.251, P=0.003) and VEGF (the first injection: β=1.875, P<0.001; the second injection: β=2.119, P<0.001) had linear relationships with CMT. Conclusion: The decrease of NLRP3 inflammasome and its products in aqueous humor may be related to the improvement of macular structure in wAMD patients after anti-VEGF therapy.
目的： 探讨核苷酸结合寡聚化结构域样受体蛋白3（NLRP3）炎症小体表达与湿性年龄相关性黄斑变性（wAMD）抗血管内皮生长因子（VEGF）治疗后黄斑结构改善的关系。 方法： 自身前后对照研究。选取2019年8月至2021年12月山东第一医科大学附属人民医院眼科收治的wAMD患者110例（110眼），玻璃体注射抗VEGF药物（雷珠单抗或贝伐单抗）治疗，收集患者房水，采用荧光定量PCR技术检测房水中NLRP3、半胱氨酸天冬氨酸蛋白酶1（Caspase-1）、凋亡相关斑点样蛋白（ASC）及白细胞介素（IL）1β的mRNA水平，酶联免疫吸附（ELISA）法检测房水中IL-1β、IL-18、肿瘤坏死因子α（TNF-α）及VEGF水平，分析上述指标与wAMD患者中心黄斑厚度（CMT）的相关性。 结果： 纳入110例wAMD患者，男68例，女42例，年龄（68.7±7.6）岁。与治疗前比较，wAMD患者注药1针和注药2针后房水中NLRP3（1.65±0.27、1.34±0.19比1.97±0.23，均P<0.017）、Caspase-1（1.47±0.15、1.29±0.17比1.53±0.18，均P<0.017）、ASC（1.33±0.14、1.21±0.18比1.47±0.12，均P<0.017）、IL-1β（1.78±0.21、1.46±0.17比2.21±0.24，均P<0.017）mRNA水平及IL-1β［（26.9±5.7）、（20.3±4.6）比（33.6±8.3）ng/L，均P<0.017］、IL-18［（32.7±7.6）、（23.3±6.9）比（46.4±9.4）ng/L，均P<0.017］、TNF-α［（39.4±6.6）、（21.7±6.3）比（52.9±9.1）ng/L，均P<0.017］、VEGF［（35.7±10.2）、（23.4±6.7）比（65.4±19.3）ng/L，均P<0.017］水平均降低，且注药2针后上述指标均低于注药1针后（均P<0.017）。多重线性回归分析结果显示，注药后NLRP3 mRNA（注药1针β=53.750，P<0.001；注药2针β=94.648，P<0.001）、IL-1β（注药1针β=1.356，P=0.021；注药2针β=2.008，P=0.003）、IL-18（注药1针β=1.984，P<0.001；注药2针β=1.251，P=0.003）及VEGF（注药1针β=1.875，P<0.001；注药2针β=2.119，P<0.001）水平与CMT呈线性关系。 结论： 房水中NLRP3炎症小体及其产物表达降低可能与wAMD患者抗VEGF治疗后黄斑结构的改善有关。.