A mass spectrometry-based strategy allows signature metabolite identification in tear fluid from people with diabetic cataracts
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.
Authors
- Weikang Shu (ORCID: https://orcid.org/0009-0004-6803-2815)
- Ziheng Qi (ORCID: https://orcid.org/0000-0002-5494-2613)
- Jiaxin Hou (ORCID: https://orcid.org/0000-0003-2703-3673)
- Jingjing Wan (ORCID: https://orcid.org/0000-0001-9324-2647)
- Wen-Ying Zhuang (ORCID: https://orcid.org/0000-0002-1162-9678)
- Miao Wang (ORCID: https://orcid.org/0000-0001-6540-6958)
- Tao Guo (ORCID: https://orcid.org/0000-0001-6808-064X)
- Shunxiang Li (ORCID: https://orcid.org/0009-0008-3967-0366)
- Yanhui Wang (ORCID: https://orcid.org/0000-0002-3214-2711)
- Xianqun Fan (ORCID: https://orcid.org/0000-0002-9394-3969)
- Yinbing Zhao
- Xiaonan Chen (ORCID: https://orcid.org/0009-0008-2799-905X)
- Yingying Lin (ORCID: https://orcid.org/0009-0008-7341-8260)
- Yating Wang (ORCID: https://orcid.org/0009-0007-7127-4825)
- Yun Su (ORCID: https://orcid.org/0000-0003-1286-7050)
- Chenxi Yan (ORCID: https://orcid.org/0000-0003-2837-3979)
Institutions
- Shanghai University (CN)
- Shanghai Jiao Tong University (CN)
- Shanghai Ninth People's Hospital (CN)
- Shanghai Institute of Hematology (CN)
- Shanghai Clinical Research Center (CN)
- East China Normal University (CN)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-11-21
- DOI
- https://doi.org/10.1038/s41467-025-65082-7
- Primary Topic
- Connexins and lens biology
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Natural Science Foundation of China
- Science and Technology Commission of Shanghai Municipality
- Shanghai Jiao Tong University
- School of Medicine, Shanghai Jiao Tong University
- National Key Research and Development Program of China