Abstract
Diabetic retinopathy (DR) is a common microvascular complication caused by diabetes mellitus (DM) and is a leading cause of vision impairment and loss among adults. Here, we performed a comprehensive proteomic analysis to discover biomarkers for DR. First, to identify biomarker candidates that are specifically expressed in human vitreous, we performed data-mining on both previously published DR-related studies and our experimental data; 96 proteins were then selected. To confirm and validate the selected biomarker candidates, candidates were selected, confirmed, and validated using plasma from diabetic patients without DR (No DR) and diabetics with mild or moderate nonproliferative diabetic retinopathy (Mi or Mo NPDR) using semiquantitative multiple reaction monitoring (SQ-MRM) and stable-isotope dilution multiple reaction monitoring (SID-MRM). Additionally, we performed a multiplex assay using 15 biomarker candidates identified in the SID-MRM analysis, which resulted in merged AUC values of 0.99 (No DR versus Mo NPDR) and 0.93 (No DR versus Mi and Mo NPDR). Although further validation with a larger sample size is needed, the 4-protein marker panel (APO4, C7, CLU, and ITIH2) could represent a useful multibiomarker model for detecting the early stages of DR.
Highlights
Diabetic retinopathy (DR) is a common microvascular complication caused by diabetes mellitus (DM) and is a leading cause of vision impairment and loss among adults [1]
We sorted patients that had no complications from diabetes except diabetic retinopathy and, all patients in this study have no kidney diseases like diabetic nephropathy
To examine whether any other factors could interfere with the multiple reaction monitoring (MRM) analysis, we carried out ANOVA tests for age, DM duration, and HbAlc and used chi-square tests for gender and hypertension (Supplementary Table 2)
Summary
Diabetic retinopathy (DR) is a common microvascular complication caused by diabetes mellitus (DM) and is a leading cause of vision impairment and loss among adults [1]. It affects more than 90% of diabetic patients to some degree. The manifestations of PDR include vitreous hemorrhage, formation of fibrous periretinal tissue accompanying neovascularization, traction retinal detachment, and, total vision loss [5, 6]. The control of systemic risk factors, such as hyperglycemia, hypertension, and dyslipidemia [7], has been shown to improve clinical therapies for diabetes-induced vision loss, more effective clinical therapies for DR patients are needed
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