Proteomic Analysis of Aqueous Humor Reveals Changes in Extracellular
Matrix Pathways in Proliferative Diabetic Retinopathy Patients Treated
with Intravitreal Ranibizumab
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.