Quantitative analysis of metabolites in glucose metabolism in the aqueous humor of patients with central retinal vein occlusion
Quantitative analysis of metabolites in glucose metabolism in the aqueous humor of patients with central retinal vein occlusion
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视网膜中央静脉阻塞患者房水中糖代谢代谢物的定量分析
DOI：
10.1016/j.exer.2020.107919
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发表时间：
2020-02-01
影响因子：
3.4
通讯作者：
Han, Guoge
中科院分区：
文献类型：
--
作者：
Wei, Pinghui;He, Meiqin;Han, Guoge
通过定量分析房水（AH）来观察视网膜中央静脉阻塞（CRVO）患者的葡萄糖代谢，并探讨抗血管内皮生长因子（VEGF）治疗后的代谢变化。从35例患者中采集AH样本。诊断为CRVO的参与者（n = 15）与接受白内障手术的参与者（n = 20）进行比较。13名CRVO患者接受了第二轮抗vegf治疗。采用超高效液相色谱串联质谱法（UHPLC-MS/MS）定量测定AH的代谢产物。采用光谱域光学相干断层扫描测量中央黄斑厚度（CMT）和视网膜神经节细胞层厚度（RGC）。确定了13种参与葡萄糖代谢的代谢物。在这些代谢物中，CRVO组琥珀酸盐、谷氨酸盐和谷氨酰胺显著降低（p分别= 0.028、0.009和0.017）。对照组（r = 0.922, p < 0.001）和CRVO组(r = 0.674, p = 0.006) α -酮戊二酸盐/柠檬酸盐（K/C）比值与谷氨酰胺水平均呈显著正相关。玻璃体内抗vegf给药后乳酸水平显著升高（t = 2.273, p = 0.045）；CMT的变化与这种增加呈负相关（r = -0.745, p = 0.003）。RGC厚度的改变与谷氨酰胺（r = -0.619, p = 0.024）和葡萄糖（r = -0.754, p = 0.003）的升高呈负相关。这些结果表明，与葡萄糖代谢相比，谷氨酰胺在CRVO患者的AH中显著降低，因此可能作为CRVO治疗的潜在靶点。玻璃体内注射抗vegf后糖酵解通路可能增强，这是了解CRVO病理生理的重要线索。
Quantitative analysis of aqueous humor (AH) was performed to investigate glucose metabolism in patients with central retinal vein occlusion (CRVO), and to explore metabolic changes after anti-vascular endothelial growth factor (VEGF) treatment. AH samples were collected from 35 patients. Participants diagnosed with CRVO (n = 15) were compared to participants who underwent cataract surgery (n = 20). Thirteen of the participants with CRVO received second-round anti-VEGF treatments. Ultra-high performance liquid chromatography tandem-mass spectrometry (UHPLC-MS/MS) was used to quantify metabolites of the AH. Central macular thickness (CMT) and retinal ganglion cell layer (RGC) thickness were measured using spectral-domain optical coherence tomography. Thirteen metabolites involved in glucose metabolism were identified. Among these metabolites, succinate, glutamate, and glutamine were significantly decreased for the CRVO group (p = 0.028, 0.009, and 0.017, respectively). The alpha-ketoglutarate/citrate (K/C) ratio had a significant positive correlation with glutamine levels for both control (r = 0.922, p < 0.001) and CRVO groups (r = 0.674, p = 0.006). A significant increase in lactate was observed after intravitreal anti-VEGF administration (t = 2.273, p = 0.045); the change in CMT was negatively correlated with this increase (r = -0.745, p = 0.003). The alteration of RGC thickness was negatively correlated with increases in both glutamine (r = -0.619, p = 0.024) and glucose (r = -0.754, p = 0.003). These results indicate that, compared to glucose metabolism, glutamine was significantly decreased in the AH of patients with CRVO, and may therefore serve as a potential target for CRVO therapy. The glycolytic pathway might be enhanced after intravitreal anti-VEGF injection, which is an important insight into CRVO pathophysiology.