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玻璃体液中的代谢组学生物标志物:揭示糖尿病视网膜病变进展的分子图景。

Metabolomic biomarkers in vitreous humor: unveiling the molecular landscape of diabetic retinopathy progression.

作者信息

Hiller John Kim, Sandås Elise Mørk, Rootwelt Helge, Vassli Anja Østeby, Lumi Xhevat, Moe Morten Carstens, Utheim Tor Paaske, Elgstøen Katja Benedikte Prestø, Petrovski Goran

机构信息

Center for Eye Research and Innovative Diagnostics, Department of Ophthalmology, Institute of Clinical Medicine, Faculty of Medicine, Oslo University Hospital, University of Oslo, Kirkeveien 166, Oslo, 0450, Norway.

Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway.

出版信息

Int J Retina Vitreous. 2025 May 22;11(1):58. doi: 10.1186/s40942-025-00682-5.

Abstract

BACKGROUND

Diabetic retinopathy (DR) is a progressive retinal disease that leads to vision loss if not detected early. Metabolomic analysis of vitreous humor offers a promising approach to identifying biomarkers associated with disease onset and progression. This pilot study investigates the metabolomic profiles of vitreous humor from patients at different stages of DR, aiming to uncover potential biomarkers for early detection and monitoring of disease progression.

METHODS

Vitreous samples were collected during therapeutic pars plana vitrectomy of 23 patients without diabetes (CTRL), with diabetes and without retinopathy (DIA), non-proliferative DR (NPDR) and proliferative DR (PDR). Metabolomics was performed using high-performance liquid chromatography coupled with high-resolution mass spectrometry.

RESULTS

Principal component analysis revealed distinct metabolic signatures differentiating the patient groups. Lysine, proline, and arginine levels progressively increased from DIA to NPDR and PDR stages, highlighting their association with disease progression. Methionine and threonine showed notable increases in PDR compared to all other groups, while carnitine, a key metabolite in lipid metabolism, exhibited stage-specific increases, peaking in PDR. The detection of systemic and topical drugs, including metformin and tropicamide, in the vitreous further emphasizes altered ocular permeability in DR.

CONCLUSION

Our findings suggest that metabolomic profiling could provide valuable insights into the underlying pathogenesis of DR and serve as a foundation for personalized therapeutic strategies.

摘要

背景

糖尿病视网膜病变(DR)是一种进行性视网膜疾病,若不及早发现会导致视力丧失。玻璃体液的代谢组学分析为识别与疾病发生和进展相关的生物标志物提供了一种有前景的方法。这项初步研究调查了不同DR阶段患者玻璃体液的代谢组学特征,旨在发现用于疾病早期检测和进展监测的潜在生物标志物。

方法

在23例无糖尿病(对照组)、有糖尿病但无视网膜病变(糖尿病组)、非增殖性DR(NPDR)和增殖性DR(PDR)患者的治疗性玻璃体切割术中收集玻璃体液样本。使用高效液相色谱结合高分辨率质谱进行代谢组学分析。

结果

主成分分析揭示了区分患者组的不同代谢特征。赖氨酸、脯氨酸和精氨酸水平从糖尿病组到NPDR和PDR阶段逐渐升高,突出了它们与疾病进展的关联。与所有其他组相比,蛋氨酸和苏氨酸在PDR中显著增加,而肉碱作为脂质代谢中的关键代谢物,呈现出阶段特异性增加,在PDR中达到峰值。在玻璃体液中检测到全身和局部药物,包括二甲双胍和托吡卡胺,进一步强调了DR中眼通透性的改变。

结论

我们的研究结果表明,代谢组学分析可为DR的潜在发病机制提供有价值的见解,并为个性化治疗策略奠定基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd9c/12096489/2eb34e77345f/40942_2025_682_Fig1_HTML.jpg

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