Aqueous Fibronectin Correlates With Severity of Macular Edema and Visual Acuity in Patients With Branch Retinal Vein Occlusion: A Proteome Study

PURPOSE: Large-scale protein analysis may bring important insights into molecular changes following branch retinal vein occlusion (BRVO). Using proteomic techniques this study compared aqueous humor samples from patients with BRVO to age-matched controls. METHODS: Aqueous humor samples from treatment naive patients with BRVO complicated by macular edema (n = 19) and age-matched controls (n = 18) were analyzed with label-free quantification nano liquid chromatography – tandem mass spectrometry (LFQ nLC-MS/MS). The severity of macular edema was measured as central retinal thickness (CRT) with optical coherence tomography. Control samples were obtained prior to cataract surgery. Proteins were filtered by requiring quantification in at least 50% of the samples in each group without imputation of missing values. Significantly changed proteins were identified with a permutation-based calculation with a false discovery rate at 0.05. RESULTS: In BRVO, 52 proteins were differentially expressed. Regulated proteins were involved in cell adhesion, coagulation, and acute-phase response. Apolipoprotein C-III, complement C3, complement C5, complement factor H, fibronectin, and fibrinogen chains were increased in BRVO and correlated with CRT. Fibronectin also correlated with best corrected visual acuity (BCVA) and vascular endothelial growth factor (VEGF). Monocyte differentiation antigen CD14 (CD14) and lipopolysaccharide-binding protein (LBP) were upregulated in BRVO. Contactin-1 and alpha-enolase were downregulated in BRVO and correlated negatively with CRT. CONCLUSIONS: Multiple proteins, including complement factors, fibrinogen chains, and apolipoprotein C-III, correlated with CRT, indicating a multifactorial response. Fibronectin correlated with BCVA, CRT, and VEGF. Fibronectin may reflect the severity of BRVO. The proinflammatory proteins CD14 and LBP were upregulated in BRVO.