2材料和方法. Materials and methods 3.结果. Results 4.讨论. Discussion



1.介绍. Introduction
Glaucoma is a leading cause of irreversible blindness and an important public health concern. Better understanding of its pathophysiology is important because it might lead to earlier detection and im- proved management strategies. Glaucoma and intraocular pressure (IOP) are tightly correlated genetically and epidemiologically ，but our understanding of cell and tissuelevel processes underlying elevated IOP and glaucoma are not well understood.
The mean IOP was calculated from four readings (two from each eye). Subjects who were receiving IOP-lowering medications or had IOPal- tering surgery were excluded from the analyses.
抗坏血酸代谢物参 与一般人群的眼内压控制
Ascorbic acid metabolites are involved in intraocular pressure control in the general population
主讲人：管浩丞 小组成员：管浩丞，高爽博，徐全兴，王家豪， 王梦幡，刘少慧，李茹月，董绮雯


我们显示O-甲基抗 坏血酸，一种循环 的维生素C代谢物， 具有显着的降低IOP 的作用，与先前对 抗坏血酸化合物的 抗高血压和抗氧化 作用的知识一致。 这些结果增强了对 IOP 控制的理解， 并可能潜在地进行 未来的IOP治疗并减 少青光眼的视力丧 失。
目录

1.介绍. Introduction

2.材料和方法. Materials and methods
The IOP measurements were taken using a non-contact air-puff tonometer (Ocular Response


Analyzer, ORA, Reichert, Buffalo, NY).
摘要
Elevated intraocular pressure (IOP) is an important risk factor for glaucoma. Mechanisms involved in its homeostasis are not well understood, but associations between metabolic factors and IOP have been reported. To investigate the relationship between levels of circulating metabolites and IOP, we performed a metabolome-wide association using a machine learning algorithm, and then employing Mendelian Randomization models to fur- ther explore the strength and directionality of effect of the metabolites on IOP.
使用非接触式空气pu 进行IOP测量 眼压计 （Ocular Response Analyzer，ORA， Reichert，Bualo， NY）。 从四个读数 （每只眼睛两个）计 算平均IOP。接受降眼 压药物治疗或进行IOP 改变手术的受试者被 排除在分析之外。
2.2代谢物测量Metabolite measurements
The eyes share cellular metabolic pathways and physiological mechanisms with other organs and tissues. Genes associated with IOP and POAG are involved, among others, in systemic lipid metabolism ，lysosomal endocytosis and angiogenesis . Additionally, both IOP and POAG are strongly associated with the components of the metabolic syndrome (hyperglycemia, hyperlipidemia and high systemic blood pressure).
2.1
人 口 和 科 目
This is a volunteer cohort recruited from the general population in the United Kingdom . Included in this study are 1763 adults (684 twin pairs and 395 singletons), for whom both metabolite levels (代谢水平)and eye measurements including IOP were available.


青光眼是不可逆转失明 的主要原因，也是重要 的公共卫生问题。 更 好地了解其病理生理学 非常重要，因为它可能 会导致更早发现和改进 管 理策略。 青光眼和 眼压（IOP）在遗传学 和流行病学上密切相关 但 是，我们对眼压和 眼压升高的细胞和组织 水平过程的理解尚不清 楚。
1.介绍. Introduction
Non-targeted metabolite detection and quantification was con- ducted using the platform provided by Metabolon Inc. (Durham, USA) on fasting plasma samples as previously described . Quality control steps for the 529 measured metabolites are reported elsewhere , and they included batch-effect data normalization, outlier (> 4 SD) removal and subsequently inverse-normalization . Only 313 me- tabolites that were measured in at least 90% of subjects were included in analyses.

2.3统计分析. Statistical analyses

2.3.1 随即森林分析代谢物对IOP的影响

Here, we employed a Random Forest (随机森林) machine learning technique (RF) (机器学习技术) which agnosti- cally identifies the metabolites that are most influential over an outcome, regardless of the specific model through which the effect is mediated. These models implicitly capture higher order interactions between variables （变量）. We used RF to rank all available metabolites according to the Breiman-Cutler “VIMP” values . Importance ranking has no associated probabilities, or formal thresholds of sig- nificance, nor any need for multiple-testing correction as long as all variables are tested jointly at the same time. To control for bias from predictor variables’ (metabolites) differing variances , all variables were standard inverse-normalized as previously described .
升高的眼压（IOP）是 青光眼的重要危险因素。 涉及其体内平衡的机制 尚不清楚，但已报道了 代谢因子和IOP之间的 关联。 为了研究循环代 谢物水平与IOP之间的 关系，我们使用机器学 习算法进行代谢组范围 的关联，然后使用孟德 尔随机化模型进一步探 索代谢物在IOP上的强 度和方向性。
摘要
We show that Omethylascorbate, a circulating Vitamin C metabolite, has a significant IOP-lowering effect, consistent with previous knowledge of the anti-hypertensive and antioxidative role of ascorbate compounds. These results enhance understanding of IOP control and may potentially benefit future IOP treatment and reduce vision loss from glaucoma.