S100A Family Proteins and Mesothelin in Tear Proteome Are Associated With Retinal Vein Occlusion
Abstract Tear samples were collected from 88 subjects and analyzed using absolute quantitative and comparative proteomic approach. We found a large proportion (505 proteins) of tear proteome between healthy donors and subjects with retinal vein occlusion (RVO). Comparative proteomic analysis revealed 30 proteins (p<0.05) significantly differed in their quantitative property. Among them S100A6 (3.7 fmoles/ng, p<0.001), S100A8 (0.68 fmoles/ng, p<0.001), and S100A9 (2.06 fmoles/ng, p<0.001) are the most overrepresented proteins. Mesothelin was found as tear-specific protein with significant increase (1.08 fmoles/ng versus 0.54 fmoles/ng in the control, p<0.001) in the RVO group. The selected altered proteins were combined to reconstruct the customized map of protein-protein interactions with the burden of quantitating property and the context of RVO-related association. The customized interactions map (FDR<0.01) emerged inflammation and impartment of retinal hemostasis as the main RVO-associated processes. The semantic analysis of customized map encouraged the prevalence of core biological processes encompassing dysregulation of mitochondrial organization and utilization of topologically incorrect folded proteins as a consequence of oxidative stress and inflammation caused by the retinal ischemic condition. Significantly differed proteins (S100A6, S100A8, S100A9, MSL, B2M) were applied for the ROC plotting with AUC varied from 0.772 to 0.952 suggesting their association with the CRVO.