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

Abstract

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 labelfree 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.

Intra-population differences of apolipoproteins in the aqueous humor

“…Increased APOC3 levels have been observed in patients with branch retinal vein occlusion with macular edema. It is proposed as interrelating with inflammatory processes [ 53 ]. Other studies have also elucidated a linkage between POAG and APOC3 [ 10 , 27 , 54 ].…”

The association of neutrophil–lymphocyte ratio and platelet–lymphocyte ratio with retinal vein occlusion: a systematic review and meta‐analysis

“…Additionally, aqueous markers of platelet activation are elevated in RVO (Cehofski et al. 2020). The relationship between NLR and PLR with many RVO risk factors explored in this paragraph is well established; our study supports an association between NLR and PLR with RVO itself.…”

Circulating microvesicles and exosomes in small cell lung cancer by quantitative proteomics

“…The samples were lysed and solubilized in 5% sodium dodecyl sulfate containing 50 mM triethylammonium bicarbonate, pH 7.55. Alkylation and tryptic digestion were performed using S-TrapTM Micro Spin Columns (Protifi, NY, USA) essentially as previously described [ 16 ]. Proteins were cleaved using PierceTM Trypsin protease, MS Grade (Thermo Fisher Scientific, Waltham, MA, USA) and peptide concentrations were measured by fluorescence using an EnSpire microplate reader (Perkin Elmer, Waltham, MA, USA).…”