Vitreous Fibronectin and Fibrinogen Expression Increased in Eyes With Proliferative Diabetic Retinopathy After Intravitreal Anti-VEGF Therapy.

Abstract

To evaluate vitreous humor (VH) protein expression profiles in patients with proliferative diabetic retinopathy (PDR), with and without intravitreal injection (IVI) of anti-vascular endothelial growth factor (anti-VEGF) before vitrectomy. We enrolled consecutive PDR patients who needed pars plana vitrectomy (PPV) with or without IVI or pan-retinal photocoagulation (PRP). Visual acuity, duration, and treatment of diabetes mellitus, ocular treatment history, and fundus examinations were recorded. VH samples were collected without artificial humor infusion. Label-free quantitative proteomics analysis was performed to determine the protein expression profiles of VH samples. Enzyme-linked immunosorbent assays were performed to validate the proteomics results. PDR patients who underwent IVI at a mean of 5.8 days (range, 3-8 days) before PPV (IVI group, n = 12) were younger than PDR patients with a history of PRP (PRP group, n = 29) and untreated PDR patients (control group, n = 21). The duration of diabetes mellitus was similar in the three groups. Label-free quantitative proteomics analysis showed that the signal intensities for fibronectin, fibrinogen α chain, fibrinogen β chain, fibrinogen γ chain, VEGF receptor 1 (VEGFR1), and VEGFR2 were significantly greater in the IVI group than in the other two groups. Enzyme-linked immunosorbent assays validated the results for fibronectin and fibrinogens, but found no significant differences in VEGF or VEGFR2 concentrations. VEGFR1 expression was significantly greater in the IVI and PRP groups than in the control group. VH fibronectin and fibrinogen concentrations were highest in the IVI patients, which may promote fibrin-fibronectin complexation and fibrosis in eyes with PDR.