Department of Ophthalmology, Icahn School of Medicine at Mount Sinai, New York, New York, United States.
NIHR Biomedical Research Centre at Moorfields Eye Hospital & UCL Institute of Ophthalmology, London, United Kingdom.
Invest Ophthalmol Vis Sci. 2023 Aug 1;64(11):11. doi: 10.1167/iovs.64.11.11.
The purpose of this study was to assess metabolites associated with intraocular pressure (IOP) and inner retina structure.
We cross-sectionally assessed 168 non-fasting plasma metabolites measured by nuclear magnetic resonance (NMR) spectroscopy with IOP (n = 28,195), macular retinal nerve fiber layer thickness (mRNFL; n = 10,584), and macular ganglion cell inner plexiform layer thickness (mGCIPL; n = 10,554) in the UK Biobank. We used multiple linear regression models adjusting for various covariates with probit-transformed metabolite levels as predictors for each outcome. Each estimate represents the difference in outcome variable per standard deviation increase in the probit-transformed metabolite values. We used the number of effective (NEF) tests and false discovery rate (FDR) to adjust for multiple comparisons for metabolites and metabolite classes, respectively.
In individual metabolite analysis, multiple amino acids, especially branched-chain amino acids, were associated with lower IOP (-0.12 mm Hg; 95% confidence interval = -0.16 to -0.07; NEF = 2.7E-05). Albumin, 3 hydroxybutyrate, lactate, and several lipids were associated with higher IOP (range = 0.07 to 0.18 mm Hg, NEF = ≤ 0.039). In IOP-adjusted analyses, five HDL-related metabolites were associated with thinner mRNFL (-0.15 microns for all metabolites, NEF = ≤ 0.027), whereas five LDL-related metabolites were associated with thicker mGCIPL (range = 0.17 to 0.20 microns; NEF = ≤ 0.044). In metabolite class analysis, the lipid components of lipoproteins (cholesterol, triglycerides, etc.) were not associated with our outcomes (FDR > 0.2 for all); yet multiple lipoproteins were significantly (FDR < 0.05) associated with all outcomes.
Branched-chain amino acids were associated with lower IOP, HDL metabolites were associated with thinner mRNFL, and LDL metabolites were associated with thicker mGCIPL.
本研究旨在评估与眼内压（IOP）和内视网膜结构相关的代谢物。
我们通过磁共振（NMR）光谱法对英国生物库中 28195 名参与者的非空腹血浆代谢物（n=28195）、10584 名参与者的黄斑视网膜神经纤维层厚度（mRNFL；n=10584）和 10554 名参与者的黄斑神经节细胞内丛状层厚度（mGCIPL；n=10554）进行了横断面评估。我们使用多元线性回归模型，根据不同的协变量调整概率转换后的代谢物水平作为每个结果的预测因子。每个估计值代表在概率转换后的代谢物值增加一个标准差的情况下，结果变量的差异。我们使用有效（NEF）检验的数量和假发现率（FDR）分别调整代谢物和代谢物类别的多重比较。
在个体代谢物分析中，多种氨基酸，特别是支链氨基酸，与较低的 IOP 相关（-0.12mmHg；95%置信区间=-0.16 至-0.07；NEF=2.7E-05）。白蛋白、3-羟基丁酸、乳酸和几种脂质与较高的 IOP 相关（范围=0.07 至 0.18mmHg，NEF=≤0.039）。在调整 IOP 的分析中，五种与高密度脂蛋白相关的代谢物与较薄的 mRNFL 相关（所有代谢物的-0.15 微米，NEF=≤0.027），而五种与低密度脂蛋白相关的代谢物与较厚的 mGCIPL 相关（范围=0.17 至 0.20 微米；NEF=≤0.044）。在代谢物类别分析中，脂蛋白的脂质成分（胆固醇、甘油三酯等）与我们的结果无关（FDR>0.2 所有）；然而，多种脂蛋白与所有结果显著相关（FDR<0.05）。
支链氨基酸与较低的 IOP 相关，高密度脂蛋白代谢物与较薄的 mRNFL 相关，而低密度脂蛋白代谢物与较厚的 mGCIPL 相关。
