Department of Ophthalmology, Faculty of Medicine, Shimane University, Izumo 693-8501, Japan.
Computational Bio Big Data Open Innovation Laboratory (CBBD-OIL), National Institute of Advanced Industrial Science and Technology, Tokyo 100-0004, Japan.
Molecules. 2022 Mar 29;27(7):2215. doi: 10.3390/molecules27072215.
We previously proposed the total assessment of hydroxylinoleates (HODEs) by LC-MS/MS after saponification and reduction of the biologic samples as biomarkers to investigate pathogenesis, disease progression, and prognosis. In this study, HODE levels were estimated in aqueous humor (AH) samples from 63 eyes (41 Japanese subjects; 15 men; mean age, 77.3 ± 6.8 years) with primary open-angle glaucoma (POAG) or cataracts. The correlations between intraocular HODE levels and background parameters, including intraocular pressure (IOP), were analyzed to assess the possible involvement of oxidative stress in glaucoma pathology. Univariate analyses showed that linoleic acid (LA) ( = 0.034) and arachidonic acid (AA) ( = 0.0041) levels were associated negatively with age; 13-(Z,E)-HODE ( = 0.018) and 13-(E,E)-HODE ( = 0.021) were associated positively with IOP; 9-(Z,E)-HODE ( = 0.039), 13-(Z,E)-HODE ( = 0.021), totally assessed-HODE (t-HODE, = 0.023), LA ( = 0.0080), and AA ( = 0.0051) were higher in eyes with glaucoma than cataract. No gender differences were seen. A mixed-effect regression model showed that higher 13-(Z,E)-HODE ( = 0.0040) and higher t-HODE ( = 0.040) were associated with glaucoma rather than cataracts; and higher levels of 13-(Z,E)-HODE/LA ( = 0.043), 13-(E,E)-HODE/LA ( = 0.042), 13-(Z,E)-HODE ( = 0.0054), and 13-(E,E)-HODE ( = 0.027) were associated with higher IOP. Linoleate-derived oxidation products were quantified successfully in AH samples from patients with glaucoma and cataracts. A free radical oxidation mechanism can be associated with IOP elevation, while enzymatic oxidation may be involved, specifically, in the pathogenesis of POAG.
我们之前提出了通过 LC-MS/MS 对生物样本进行皂化和还原后羟基亚麻酸（HODEs）的总量评估作为研究发病机制、疾病进展和预后的生物标志物。在这项研究中，我们在来自 63 只眼睛（41 名日本受试者；15 名男性；平均年龄 77.3 ± 6.8 岁）的房水中估计了 HODE 水平，这些眼睛患有原发性开角型青光眼（POAG）或白内障。分析了眼内 HODE 水平与包括眼压（IOP）在内的背景参数之间的相关性，以评估氧化应激在青光眼发病机制中的可能作用。单变量分析表明，亚油酸（LA）（ = 0.034）和花生四烯酸（AA）（ = 0.0041）水平与年龄呈负相关；13-（Z，E）-HODE（ = 0.018）和 13-（E，E）-HODE（ = 0.021）与 IOP 呈正相关；9-（Z，E）-HODE（ = 0.039），13-（Z，E）-HODE（ = 0.021），总评估-HODE（t-HODE， = 0.023），LA（ = 0.0080）和 AA（ = 0.0051）在青光眼眼中高于白内障。未观察到性别差异。混合效应回归模型显示，较高的 13-（Z，E）-HODE（ = 0.0040）和较高的 t-HODE（ = 0.040）与青光眼相关，而不是白内障；较高的 13-（Z，E）-HODE/LA（ = 0.043），13-（E，E）-HODE/LA（ = 0.042），13-（Z，E）-HODE（ = 0.0054）和 13-（E，E）-HODE（ = 0.027）与较高的 IOP 相关。成功地在青光眼和白内障患者的房水样本中定量了亚油酸衍生的氧化产物。自由基氧化机制可能与眼压升高有关，而酶促氧化可能涉及 POAG 的发病机制。
