scholarly journals Development of Diagnostic Biomarkers for Detecting Diabetic Retinopathy at Early Stages Using Quantitative Proteomics

2016 ◽  
Vol 2016 ◽  
pp. 1-22 ◽  
Author(s):  
Jonghwa Jin ◽  
Hophil Min ◽  
Sang Jin Kim ◽  
Sohee Oh ◽  
Kyunggon Kim ◽  
...  

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.

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Olga Simó-Servat ◽  
Rafael Simó ◽  
Cristina Hernández

Diabetic retinopathy (DR) is the main cause of working-age adult-onset blindness. The currently available treatments for DR are applicable only at advanced stages of the disease and are associated with significant adverse effects. In early stages of DR the only therapeutic strategy that physicians can offer is a tight control of the risk factors for DR. Therefore, new pharmacological treatments for these early stages of the disease are required. In order to develop therapeutic strategies for early stages of DR new diagnostic tools are urgently needed. In this regard, circulating biomarkers could be useful to detect early disease, to identify those diabetic patients most prone to progressive worsening who ought to be followed up more often and who could obtain the most benefit from these therapies, and to monitor the effectiveness of new drugs for DR before more advanced DR stages have been reached. Research of biomarkers for DR has been mainly based on the pathogenic mechanism involved in the development of DR (i.e., AGEs, oxidative stress, endothelial dysfunction, inflammation, and proangiogenic factors). This review focuses on circulating biomarkers at both early and advanced stages that could be relevant for the prediction or detection of DR.


2013 ◽  
Vol 12 (3) ◽  
pp. 1078-1089 ◽  
Author(s):  
Kyunggon Kim ◽  
Sang Jin Kim ◽  
Dohyun Han ◽  
Jonghwa Jin ◽  
Jiyoung Yu ◽  
...  

2010 ◽  
Vol 9 (2) ◽  
pp. 689-699 ◽  
Author(s):  
Kyunggon Kim ◽  
Sang Jin Kim ◽  
Hyeong Gon Yu ◽  
Jiyoung Yu ◽  
Kyong Soo Park ◽  
...  

Author(s):  
Mitsuaki Yanagida ◽  
Kensuke Hamamura ◽  
Kenji Takamori ◽  
Yoshihiko Araki

Background Hypertensive disorders of pregnancy are defined as syndromes characterized by high blood pressure that develop after 20 weeks of pregnancy. The pathogenesis of hypertensive disorders of pregnancy has not been fully elucidated, and the most effective treatment is the termination of pregnancy. Therefore, methods for an early predictive diagnosis should be developed to rescue both the mother and the child. Methods Previously, we explored the serum peptides whose concentration varied specifically between patients with hypertensive disorders of pregnancy and normal pregnant women using peptidomics analysis and identified seven candidate marker peptides. To quantify the marker peptides more reliably, we attempted to quantify these peptides simultaneously by multiple reaction monitoring using liquid chromatography/tandem mass spectrometry (LC-MRM/MS). Non-labelled and stable isotope-labelled forms of the seven peptides were synthesized as standards, and the multiple reaction monitoring transitions for their quantification were determined. Results As the retention of the peptides by the reversed-phase column was dependent on their hydrophobicity, two solvent compositions were required for the retention of all peptides. Under these conditions, we detected the peptides by LC-MRM/MS using a column-switching method. Further, we succeeded in quantifying the peptides in the serum of pregnant women using stable isotope dilution. Conclusion Our new peptidomics method has great value for peptides, particularly those that have no specific antibody as a detection tool. Using this system, the serum peptides in patients with hypertensive disorders of pregnancy can be validated as diagnostic markers of hypertensive disorders of pregnancy. Further, this method can potentially be applied to the general quantification of other serum peptides.


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