College of Pharmacy, Dankook University, Cheonan, Republic of Korea.
Center for Human Risk Assessment, Dankook University, Chungnam, Republic of Korea.
J Toxicol Environ Health A. 2021 Apr 18;84(8):313-330. doi: 10.1080/15287394.2020.1867274. Epub 2021 Jan 3.
Dry eye disease (DED) is a chronic and progressive lesion on the ocular surface and induces symptoms, such as burning sensation, itchy eyes, heavy eyes, tired eyes, dry feeling, facial flushing, and blurred vision. The present study was performed to develop DED biomarkers using metabolomics in a rat model. DED was induced by injecting scopolamine and exposing rats to a dry condition. Scopolamine (12 mg/kg/day for 7 days) was subcutaneously injected to male Sprague-Dawley rats. The rats were placed in dry condition with air-flow and dehumidifier. Tear volume and tear breakup time (TBUT) were measured, and eyes were examined through fluorescein staining to assess DED. Mucosal damage and immune reactions were also determined. Plasma and urinary endogenous metabolites were determined using H-NMR analysis. Compared with control tear and TBUT levels were significantly decreased in the DED group whereas corneal damage was significantly increased. The levels of interleukins (IL-6) and IL-1β significantly elevated in the cornea and lacrimal glands in the DED group. TNF-α was numerically increased but not significantly different between groups. Pattern recognition using principal component analysis (PCA) and orthogonal projections to latent structure-discriminant analysis (OPLS-DA) of the NMR spectra in global profiling revealed different clusters between DED and control groups. Target profiling demonstrated that PCA and OPLS-DA score plots were separated between DED and controls in plasma and urine. Subsequently, 9 plasma metabolites were selected to examine different clustering between groups, and 26 urinary metabolites were also selected. Plasma metabolites showed a non-significant rising tendency in the DED group. Urinary phenylalanine, phenylacetate, pantothenate, glycine, succinate, methanol, valine, propylene glycol, histidine, threonine, lactate, and acetate were significantly different between control and DED rats. These results may contribute to understanding the metabolic regulation that is involved in DED and might be useful for potential biomarkers related to DED in rats.
干眼症（DED）是一种眼表的慢性进行性病变，可引起烧灼感、眼痒、眼睛沉重、眼睛疲劳、干燥感、面部潮红和视力模糊等症状。本研究旨在使用代谢组学在大鼠模型中开发 DED 生物标志物。通过向大鼠注射东莨菪碱并使其处于干燥状态来诱导 DED。将东莨菪碱（每天 12mg/kg，连续 7 天）皮下注射到雄性 Sprague-Dawley 大鼠中。将大鼠置于具有气流和除湿器的干燥环境中。测量泪液体积和泪膜破裂时间（TBUT），并用荧光素染色检查眼睛以评估 DED。还确定了粘膜损伤和免疫反应。使用 H-NMR 分析测定血浆和尿内源性代谢物。与对照组相比，DED 组的泪液和 TBUT 水平明显降低，而角膜损伤明显增加。IL-6 和 IL-1β 在 DED 组的角膜和泪腺中的水平显著升高。TNF-α在两组之间的数值增加，但无统计学差异。使用主成分分析（PCA）和正交偏最小二乘法判别分析（OPLS-DA）对全局分析中的 NMR 光谱进行模式识别，结果显示 DED 组和对照组之间存在不同的聚类。靶向分析表明，在血浆和尿液中，PCA 和 OPLS-DA 得分图在 DED 组和对照组之间分离。随后，选择 9 种血浆代谢物检查两组之间的不同聚类，选择 26 种尿代谢物进行检查。在 DED 组中，血浆代谢物呈非显著上升趋势。尿苯丙氨酸、苯乙酸、泛酸、甘氨酸、琥珀酸、甲醇、缬氨酸、丙二醇、组氨酸、苏氨酸、乳酸盐和乙酸盐在对照组和 DED 大鼠之间有显著差异。这些结果可能有助于了解参与 DED 的代谢调节，并可能有助于寻找与 DED 相关的潜在大鼠生物标志物。
