Abstract
BackgroundIdiopathic 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.MethodsThis 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.ResultsThere 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.ConclusionsPatients 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.
Highlights
Idiopathic macular holes are common ophthalmic manifestations with unknown pathogenesis
Cytokine levels in aqueous humor Levels of cytokines in aqueous humor samples were compared between the Idiopathic macular holes (IMHs) and control groups (Table 2)
Twenty-seven cytokines with significant differences in levels are shown in Fig. 2a; of these 27, 20 were significantly upregulated and seven were significantly downregulated
Summary
Idiopathic macular holes are common ophthalmic manifestations with unknown pathogenesis. There has been minimal research regarding the causes of idiopathic macular holes, especially with respect to the underlying immune mechanism. Macular holes constitute tissue defects that extend from the retinal inner membrane to the photoreceptor layer of the macula, seriously impairing central vision in affected patients. Various causes of macular holes have been recognized [2]. Macular holes most frequently occur in healthy women aged > 50 years (mean age, 65 years; female: male ratio of 2:1); 6–28% of affected patients have bilateral macular holes [3]. Idiopathic macular holes (IMHs) have no obvious systemic or ocular local causes, and do not involve disease in the fundus itself. IMHs have become increasingly important in clinical practice because of the large number of older people in many countries, and the morbidity of this condition has gradually increased [4]
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