A mass spectrometry-based strategy allows signature metabolite identification in tear fluid from people with diabetic cataracts

Ziheng Qi, Miao Wang, Chenxi Yan, Yinbing Zhao, Yanhui Wang, Xiaonan Chen, Shunxiang Li, Wenbo Zhuang, Weikang Shu, Yating Wang, Yingying Lin, Jiaxin Hou, Tao Guo (), Xianqun Fan (), Yun Su () and Jingjing Wan ()
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Ziheng Qi: East China Normal University, School of Chemistry and Molecular Engineering
Miao Wang: Shanghai Jiao Tong University School of Medicine, Department of Ophthalmology, Shanghai Ninth People’s Hospital
Chenxi Yan: Shanghai Jiao Tong University School of Medicine, Department of Ophthalmology, Shanghai Ninth People’s Hospital
Yinbing Zhao: East China Normal University, School of Chemistry and Molecular Engineering
Yanhui Wang: East China Normal University, School of Chemistry and Molecular Engineering
Xiaonan Chen: East China Normal University, School of Chemistry and Molecular Engineering
Shunxiang Li: Shanghai Jiao Tong University, School of Biomedical Engineering, and Med-X Research Institute
Wenbo Zhuang: Shanghai Jiao Tong University School of Medicine, Department of Ophthalmology, Shanghai Ninth People’s Hospital
Weikang Shu: East China Normal University, School of Chemistry and Molecular Engineering
Yating Wang: East China Normal University, School of Chemistry and Molecular Engineering
Yingying Lin: East China Normal University, School of Chemistry and Molecular Engineering
Jiaxin Hou: East China Normal University, School of Chemistry and Molecular Engineering
Tao Guo: Shanghai Jiao Tong University School of Medicine, Department of Ophthalmology, Shanghai Ninth People’s Hospital
Xianqun Fan: Shanghai Jiao Tong University School of Medicine, Department of Ophthalmology, Shanghai Ninth People’s Hospital
Yun Su: Shanghai Jiao Tong University School of Medicine, Department of Ophthalmology, Shanghai Ninth People’s Hospital
Jingjing Wan: East China Normal University, School of Chemistry and Molecular Engineering

Nature Communications, 2025, vol. 16, issue 1, 1-16

Abstract: Abstract Metabolic biomarker discovery in trace body fluids remains a significant challenge, toward molecular diagnosis and pathology studies in many diseases. Especially for eye-related diseases, such an approach based on non-invasive tear fluids remains an unsatisfied urgent need in ophthalmology. Here we construct a metabolic biomarker panel from 10 nL of tear fluids in seconds using nanoparticle-enhanced laser desorption/ionization -mass spectrometry (MS), which achieves an area under the curve of 0.923 for discriminating diabetic cataracts from alone age-related cataracts. Importantly, we integrate liquid chromatography -MS into the above analysis process to construct an integrated strategy, allowing reliable metabolite annotation by nanoliter sample volume without compromising high throughput. Further, using matched aqueous humors, we identify 1,5-anhydroglucitol as a biomarker of diabetic cataracts, revealing its protective effect against high glucose-induced lens oxidative stress and opacification, as a demonstration of the metabolic reprogramming. Our approach can be universally applied to uncover biomarkers using trace body fluid, promising next-generation metabolic reprogramming identification.

Date: 2025
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DOI: 10.1038/s41467-025-65082-7

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