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Stephanie M. Ecker, Ann O. Igbre, Joshua C. Hines, Bert M. Glaser; Vitreous Biomarker Changes in the Progression from Nonproliferative to Proliferative Diabetic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2012;53(14):5771.
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© ARVO (1962-2015); The Authors (2016-present)
In this study we explore vitreous biomarker differences of Proliferative Diabetic Retinopathy (PDR), Nonproliferative Diabetic Retinopathy (NPDR) and non-diabetic controls. A group of 44 phosphorylated receptor proteins and cytokines were chosen for their importance in the key biochemical aspects of diabetic retinopathy such as angiogenesis, inflammation, apoptosis and oxidative stress.
In-office vitreous aspirates were used from 95 patients; 43 PDR, 28 NPDR and 24 non-diabetic controls. All vitreous aspirates were performed using a 25 gauge needle directed into the mid-vitreous cavity through the pars plana. A 1 mL syringe was used to aspirate 0.05-0.10 mL of vitreous fluid. Each of the 95 patient samples were probed against all 44 proteins using reverse phase protein microarray technology. Statistical analysis was done using Mann-Whitney U-test and ROC curves to determine the significantly different proteins between each of the diabetic groups and the controls. A P value of less than 0.05 and an AUC greater than 0.70 were considered significant.
PDR and NPDR share 10 proteins that are expressed at significantly different levels from non-diabetic patients, the most significant of these proteins includes αB Crystallin, C3a, COX-2 and MMP-9;. When PDR samples are compared to controls there are significant differences in AKT T308, C9, IL-10 and MMP-14; while NPDR samples compared to controls show differences in cABL, cKIT Y703, TIMP2, VEGFR2 Y951 and VEGFR2 Y1175 levels. PDR and NPDR also have significant differences in vitreous biomarker levels when compared to each other. These biomarkers include AMPK α1 S485, BCL2 T56, cABL T735, ER α S167, FGF Basic, IL-1β, MMP-9, MMP-14, TGFβ receptor, TNFα, VEGFR2 Y951 and VEGFR2 Y1175.
Vitreous protein biomarkers differ between controls and both NPDR and PDR groups. In addition, there is a subset of biomarkers that are uniquely different between NPDR and PDR. The changing levels of these biomarkers between NPDR and PDR may improve understanding of the disease process and help predict progression of NPDR to PDR.
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