Department of Ophthalmology, The Fourth Hospital of Shenyang, 110016, Shenyang, Liaoning, People's Republic of China.
University of Chinese Academy of Sciences, Beijing, People's Republic of China.
BMC Ophthalmol. 2021 Jan 11;21(1):27. doi: 10.1186/s12886-020-01782-6.
Idiopathic macular holes are common ophthalmic manifestations with unknown pathogenesis. Thus far, there has been minimal research regarding the causes of idiopathic macular holes, especially with respect to the underlying immune mechanism. To provide clarity regarding the treatment and prognosis of idiopathic macular holes, specifically regarding the levels of cytokines in affected patients, this study examined and analyzed multiple cytokine levels in aqueous humor from patients with idiopathic macular holes.
This comparative cross-sectional study included 38 patients in two groups: a cataract control group (n = 17) and an idiopathic macular hole group (n = 21). The levels of 48 cytokines in aqueous humor were detected by multiplex analysis with antibody-coupled magnetic beads. The Kolmogorov-Smirnov test was used to check whether the data were normally distributed; Student's t-test and the Mann-Whitney U test were used to assess differences in cytokine levels between the two groups. Spearman correlation analysis was used to assess relationships among cytokine levels in the experimental group. Signaling pathways containing cytokines with significantly different expression in the experimental group were identified.
There were significant differences in aqueous humor cytokine levels between patients with idiopathic macular holes and patients in the cataract control group. Notably, hepatocyte growth factor (p = 0.0001), GM-CSF (p = 0.0111), and IFN-γ (p = 0.0120) were significantly upregulated in the experimental group, while TNF-α (p = 0.0032), GRO-α (p < 0.0001), and MIF (p < 0.0001) were significantly downregulated in the experimental group. Furthermore, the GM-CSF level showed significant positive correlations with levels of IL-1 (r = 0.67904, p < 0.001), IL-4 (r = 0.76017, p < 0.001), and IFN-γ (r = 0.59922, p = 0.004097) in the experimental group. Moreover, the levels of nerve growth factor and hepatocyte growth factor showed a significant positive correlation (r = 0.64951, p = 0.001441) in the experimental group.
Patients with idiopathic macular holes showed significant variation in aqueous humor immune response after the onset of hole formation, including the recruitment of immune cells and regulation of cytokine expression. Our findings also suggest that it is not appropriate to use patients with macular holes as the control group in studies of aqueous humor cytokine levels in ophthalmic diseases.
特发性黄斑裂孔是一种常见的眼部表现，其发病机制尚不清楚。迄今为止，对于特发性黄斑裂孔的病因研究甚少，特别是其潜在的免疫机制。为了阐明特发性黄斑裂孔的治疗和预后，特别是受影响患者的细胞因子水平，本研究通过抗体偶联磁珠的多重分析检测并分析了特发性黄斑裂孔患者房水中的多种细胞因子水平。
本研究采用病例对照的横断面研究，共纳入两组 38 例患者：白内障对照组（n=17）和特发性黄斑裂孔组（n=21）。采用抗体偶联磁珠的多重分析检测房水中 48 种细胞因子的水平。采用 Kolmogorov-Smirnov 检验来检验数据是否呈正态分布；采用 Student's t 检验和 Mann-Whitney U 检验来评估两组间细胞因子水平的差异。采用 Spearman 相关分析来评估实验组中细胞因子水平之间的关系。鉴定出实验组中表达差异显著的细胞因子信号通路。
特发性黄斑裂孔患者房水中的细胞因子水平与白内障对照组患者有显著差异。值得注意的是，实验组中肝细胞生长因子（p=0.0001）、GM-CSF（p=0.0111）和 IFN-γ（p=0.0120）显著上调，而 TNF-α（p=0.0032）、GRO-α（p<0.0001）和 MIF（p<0.0001）显著下调。此外，GM-CSF 水平与实验组中 IL-1（r=0.67904，p<0.001）、IL-4（r=0.76017，p<0.001）和 IFN-γ（r=0.59922，p=0.004097）水平呈显著正相关。此外，实验组中神经生长因子和肝细胞生长因子水平呈显著正相关（r=0.64951，p=0.001441）。
特发性黄斑裂孔患者在孔形成后房水中的免疫反应发生显著变化，包括免疫细胞的募集和细胞因子表达的调节。我们的研究结果还表明，在眼部疾病房水中细胞因子水平的研究中，不应将黄斑裂孔患者作为对照组。
