2. Academic Validation
  3. A mass spectrometry-based strategy allows signature metabolite identification in tear fluid from people with diabetic cataracts

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

  • Nat Commun. 2025 Nov 21;16(1):10246. doi: 10.1038/s41467-025-65082-7.
Ziheng Qi # 1,  Miao Wang # 2 3,  Chenxi Yan # 2 3,  Yinbing Zhao 1,  Yanhui Wang 1,  Xiaonan Chen 1,  Shunxiang Li 4,  Wenbo Zhuang 2 3,  Weikang Shu 1,  Yating Wang 1,  Yingying Lin 1,  Jiaxin Hou 1,  Tao Guo 5 6,  Xianqun Fan 7 8,  Yun Su 9 10,  Jingjing Wan 11
Affiliations

Affiliations

  • 1 School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, PR China.
  • 2 Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
  • 3 Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, PR China.
  • 4 School of Biomedical Engineering, and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, PR China.
  • 5 Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China. [email protected].
  • 6 Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, PR China. [email protected].
  • 7 Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China. [email protected].
  • 8 Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, PR China. [email protected].
  • 9 Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China. [email protected].
  • 10 Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, PR China. [email protected].
  • 11 School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, PR China. [email protected].
  • # Contributed equally.
PMID: 41271624 DOI: 10.1038/s41467-025-65082-7
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.

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