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Ashok Sharma, Wenbo Zhi, Sai Karthik Kodeboyina, Shan Bai, Jin-Xiong She, Shruti Sharma; Discovery of Urinary Proteomic Changes Associated with Proliferative Diabetic Retinopathy using Mass Spectrometry Analyses. Invest. Ophthalmol. Vis. Sci. 2018;59(9):1213. doi: https://doi.org/.
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Many of the proteins commonly detected in blood are also detected in urine samples, with the potential to serve as biomarkers. Moreover, the relative ease in obtaining large quantities of samples through non-invasive means makes urine a compelling source for biomarker discovery. The purpose of this study was to discover proteomic alterations in the urine from Type 1 Diabetes (T1D) patients with proliferative diabetic retinopathy (PDR).
Urine samples from 50 T1D patients (n=21 with no diabetic complications; n=29 with PDR) from the Phenome and Genome of Diabetes Autoimmunity (PAGODA) study were analyzed using Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS). Statistical analyses were performed to discover the difference in protein levels in T1D patients with and without PDR. Bioinformatics analyses were conducted to identify biological pathways, protein interaction networks and the cellular functions of the differentially regulated proteins.
A total of 534 proteins were identified in the urine samples from 50 T1D patients. We found significant changes in the levels of 33 proteins in patients with retinopathy as compared to patients with no diabetic complications. The top 10 proteins with a significant increase in retinopathy are: CD22 (4.1-fold), S100A1 (3.8-fold), ORM1 (3.2-fold), HBA2 (2.8-fold), KRT6A (2.6-fold), CHGA (2.4-fold), SPP1 (2.3-fold), PODXL (2.3-fold), ITIL (2.3-fold), and THBS4 (2.2-fold). Bioinformatics analyses revealed that IL-6 signaling and NF-kB signaling pathways are significantly enriched in proteins associated with retinopathy. Additionally, Cell-to-cell signaling and interaction (n=15; p=2.7x10-10), cellular movement (n=14; p=3.4x10-7), cell death and survival (n=15; p=2.8 x 10-6), carbohydrate metabolism (n=6; p=5.0 x 10-6), and small molecule biochemistry (n=11; p=5.0 x 10-6) are significantly enriched biological functions in these proteins.
We found 33 urinary proteins with significant alterations in T1D patients with PDR in comparison to those with no complications. We also highlighted the functional relevance of these proteins. Particularly, IL-6 signaling and NF-kB signaling pathways were significantly enriched, reinforcing the idea that inflammation is involved in the pathogenesis of PDR. The identification of novel urine biomarkers holds translational potential for predicting PDR progression.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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