Abstract
Purpose: :
To identify novel cytokines that are upregulated in the vitreous of proliferative diabetic retinopathy (PDR) and central retinal vein occlusion (CRVO) patients compared to macular hole (MH) and macular pucker (MP) control vitreous.
Methods: :
Vitreous samples were obtained from patients undergoing vitrectomy for clinically indicated reasons. Current analysis includes 3 MP, 6 MH, 3 CRVO, and 15 PDR patients. Levels of 42 different cytokines and chemokines were analyzed in patient vitreous samples in multiplexed fashion using Magpix instrumentation featuring xMAP detection technology (EMD Millipore). Cytokine levels were evaluated via xPONENT software. Statistically significant differences between MH and PDR, and MP and PDR were determined by unpaired T-tests, whereby a p value < 0.05 was considered significant.
Results: :
Our analysis identified 18 cytokines that were significantly upregulated in the vitreous of PDR patients compared to either MH or MP vitreous samples. Among these, there were a subset of cytokines previously been shown to be altered in PDR vitreous samples, including FLT-3L, Fractalkine, GRO, IL-6, IL-8, IL-10, IP-10, MDC, and VEGF. In addition, we identified potentially novel biomarkers of PDR whose upregulation have not previously been correlated to PDR. Interestingly, not all upregulated cytokines were significantly altered from MH and MP vitreous samples. We also noted a wide range of VEGF vitreous levels among PDR patients, ranging from as low as 7.53 pg/mL to over 1000 pg/mL. Finally, we have preliminary data to indicate the presence of cytokine upregulation in CRVO patients that implicate them as novel biomarkers that distinguish disease states.
Conclusions: :
We have identified 18 out of our panel of 42 cytokines that are significantly upregulated in PDR patient vitreous compared to MH and/or MP vitreous samples. While our data is consistent with previously published reports of upregulation of some of these cytokines, we have identified a subset that potentially represents novel biomarkers of disease for both PDR and CRVO patients. These results signify not only the utility of multiplexed analysis for the identification of novel biomarkers, but also that implicate the useful pursuit of novel cytokines involved in the pathogenesis of PDR and CRVO.
Keywords: diabetic retinopathy • vitreous • cytokines/chemokines