Laíns Inês, Chung Wonil, Kelly Rachel S, Gil João, Marques Marco, Barreto Patrícia, Murta Joaquim N, Kim Ivana K, Vavvas Demetrios G, Miller John B, Silva Rufino, Lasky-Su Jessica, Liang Liming, Miller Joan W, Husain Deeba
Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA 02114, USA.
Faculty of Medicine, University of Coimbra, 3000 Coimbra, Portugal.
Metabolites. 2019 Jul 2;9(7):127. doi: 10.3390/metabo9070127.
The pathogenesis of age-related macular degeneration (AMD), a leading cause of blindness worldwide, remains only partially understood. This has led to the current lack of accessible and reliable biofluid biomarkers for diagnosis and prognosis, and absence of treatments for dry AMD. This study aimed to assess the plasma metabolomic profiles of AMD and its severity stages with the ultimate goal of contributing to addressing these needs. We recruited two cohorts: Boston, United States ( = 196) and Coimbra, Portugal ( = 295). Fasting blood samples were analyzed using ultra-high performance liquid chromatography mass spectrometry. For each cohort, we compared plasma metabolites of AMD patients versus controls (logistic regression), and across disease stages (permutation-based cumulative logistic regression considering both eyes). Meta-analyses were then used to combine results from the two cohorts. Our results revealed that 28 metabolites differed significantly between AMD patients versus controls (false discovery rate (FDR) -value: 4.1 × 10-1.8 × 10), and 67 across disease stages (FDR -value: 4.5 × 10-1.7 × 10). Pathway analysis showed significant enrichment of glycerophospholipid, purine, taurine and hypotaurine, and nitrogen metabolism (-value ≤ 0.04). In conclusion, our findings support that AMD patients present distinct plasma metabolomic profiles, which vary with disease severity. This work contributes to the understanding of AMD pathophysiology, and can be the basis of future biomarkers and precision medicine for this blinding condition.
年龄相关性黄斑变性（AMD）是全球失明的主要原因之一，其发病机制仍仅部分为人所知。这导致目前缺乏用于诊断和预后的可获取且可靠的生物流体生物标志物，以及干性AMD的治疗方法。本研究旨在评估AMD及其严重程度阶段的血浆代谢组学特征，最终目标是有助于满足这些需求。我们招募了两个队列：美国波士顿（n = 196）和葡萄牙科英布拉（n = 295）。使用超高效液相色谱质谱法分析空腹血样。对于每个队列，我们比较了AMD患者与对照组的血浆代谢物（逻辑回归），以及跨疾病阶段（考虑双眼的基于置换的累积逻辑回归）。然后进行荟萃分析以合并两个队列的结果。我们的结果显示，AMD患者与对照组之间有28种代谢物存在显著差异（错误发现率（FDR）p值：4.1×10 - 1.8×10），跨疾病阶段有67种（FDR p值：4.5×10 - 1.7×10）。通路分析显示甘油磷脂、嘌呤、牛磺酸和亚牛磺酸以及氮代谢显著富集（p值≤0.04）。总之，我们的研究结果支持AMD患者呈现独特的血浆代谢组学特征，且随疾病严重程度而变化。这项工作有助于理解AMD的病理生理学，并可为这种致盲疾病未来的生物标志物和精准医学奠定基础。
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