Comparative Tear Fluid Proteomics to Explore Treatment Responsiveness in Diabetic Macular Edema: A Pilot Study.

I-Hsin Ma, Yuan-Ling Hsu, Hsin-Yi Wu, Yi-Ting Hsieh, Szu-Hua Pan

Abstract readComparative Study

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Article in Journal of proteome research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 authors.

I-Hsin MaDepartment of Ophthalmology, National Taiwan University Hospital, Hsinchu Branch, Hsinchu 302, Taiwan.ORCID 0000-0001-5557-2039

Yuan-Ling HsuGraduate institute of medical genomics and proteomics, National Taiwan University College of Medicine, Taipei 100, Taiwan.

Hsin-Yi WuInstrumentation Center, National Taiwan University, Taipei 106, Taiwan.ORCID 0000-0003-0722-0201

Yi-Ting HsiehDepartment of Ophthalmology, National Taiwan University Hospital, Hsinchu Branch, Hsinchu 302, Taiwan.

Szu-Hua PanGraduate institute of medical genomics and proteomics, National Taiwan University College of Medicine, Taipei 100, Taiwan.ORCID 0000-0002-0138-0434

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Diabetic macular edema (DME) is a leading cause of vision loss in patients with diabetes, with variable responses to intravitreal antivascular endothelial growth factor (VEGF) therapy. This study aimed to identify tear fluid proteins linked to treatment responsiveness. Tear fluid samples were collected from 13 patients with diabetes (21 eyes with DME), among which 9 samples were analyzed using tandem mass tag-labeled liquid chromatography-mass spectrometry, and all 21 samples were validated with ELISA. Protein identification and quantification were performed using MaxQuant. Gene set enrichment analysis identified differentially expressed proteins, and an enzyme-linked immunosorbent assay was used to validate specific protein targets. Among the 3121 quantified proteins, DME-related proteins were enriched in cellular localization, oxidative stress response, and VEGFA-VEGFR2 signaling. Responders' tear fluid proteomes were linked to modulation of the extracellular matrix and inflammation, whereas nonresponders showed enrichment in inflammation and NOTCH/WNT pathways. Targeted protein analysis demonstrated that the interplay between TIMP1, MMP9, and insulin growth factor binding protein 3 (IGFBP3) correlated with treatment response. These results suggest that tear fluid proteomic analysis is a promising alternative to intraocular sampling for evaluating DME responsiveness, offering insights consistent with aqueous and vitreous proteomes while aligning with clinical prognosis and disease pathophysiology.

Indexed as

Diabetic RetinopathyEye ProteinsMacular EdemaProteomeProteomicsTearsAgedAngiogenesis InhibitorsChromatography, LiquidFemaleHumansInsulin-Like Growth Factor Binding Protein 3MaleMatrix Metalloproteinase 9Middle AgedPilot ProjectsAngiogenesis InhibitorsEye ProteinsIGFBP3 protein, humanInsulin-Like Growth Factor Binding Protein 3Matrix Metalloproteinase 9MMP9 protein, humanProteometear proteinsTIMP1 protein, humanTissue Inhibitor of Metalloproteinase-1Vascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2VEGFA protein, humanantivascular endothelial growth factordiabetic macular edemadiabetic retinopathydifferentially expressed proteinsproteometear fluids

Identifiers

PMID40882144

DOI10.1021/acs.jproteome.5c00181

PMCPMC12501991

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.