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Proteomic Analysis of Aqueous Humor Reveals Changes in Extracellular Matrix Pathways in Proliferative Diabetic Retinopathy Patients Treated with Intravitreal Ranibizumab
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  • Xiaolan Du,
  • Huan Chen,
  • Tan Wang,
  • Hanyi Min
Xiaolan Du
Chinese Academy of Medical Sciences & Peking Union Medical College
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Huan Chen
Chinese Academy of Medical Sciences & Peking Union Medical College
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Tan Wang
Chinese Academy of Medical Sciences & Peking Union Medical College
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Hanyi Min
Chinese Academy of Medical Sciences & Peking Union Medical College

Corresponding Author:[email protected]

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Abstract

Anti-VEGF therapy is commonly used to treat proliferative diabetic retinopathy (PDR), but the exact mechanism of VEGF signaling is not fully understood. Using data-independent acquisition mass spectrometry (DIA-MS), we analyzed proteomic changes in aqueous humor (AH) samples collected before and one week after intravitreal ranibizumab (IVR) treatment from 10 PDR patients to discover potential biomarkers. Resultantly, 875 proteins were quantified and 26 proteins were significantly altered in response to IVR treatment in PDR. Further investigation through gene ontology (GO) and pathway analysis revealed that these differentially expressed proteins were primarily involved in extracellular matrix (ECM) and platelet degranulation signaling. Protein-protein interaction analysis highlighted five hub proteins (COL3A1, DPT, VEGFA, SPP1, SERPING1) that were found to be ECM components. Enzyme-linked immunosorbent assay (ELISA) confirmed the decreased levels of VEGFA and increased levels of DPT proteins after IVR treatment in another 8 samples of AH in 4 PDR patients. Our study provided novel insights into aqueous proteins of PDR following IVR treatment. Targeting the ECM pathway, particularly the elevation of DPT protein, may provide a deeper understanding of the anti-VEGF resistance and VEGF signaling in PDR.
19 Sep 2023Submitted to Clinical Applications
06 Oct 2023Submission Checks Completed
06 Oct 2023Assigned to Editor
06 Oct 2023Review(s) Completed, Editorial Evaluation Pending
06 Oct 2023Reviewer(s) Assigned