Abstract
Purpose:
The purpose of this study is to explore potential proteomic biomarkers in vitreous samples of patients with different severities of proliferative diabetic retinopathy (PDR).
Methods:
Ninety six (96) in-office vitreous aspirates were obtained from 42 patients with PDR and 24 age matched non-diabetic controls. All 96 samples were probed against 44 pathway proteins using reverse phase protein microarray (RPPM) technology.
Results:
When comparing PDR patients who had visual acuity (VA) better than 20/ 200 vs. patients with VA worse than 20/200 there were 20 proteins that had significantly different levels between the 2 groups. Among these proteins, MMP-9 had significantly higher vitreous levels in patients with better VA (<20/200) vs. patients with worse VA (>20/200). Between the two groups, the statistical significance is highest for MMP-9 among the 20 proteins (P=0.006, ROC: AUC= 0.7837, P= 0.006). Those eyes with better VA demonstrated significant correlation of MMP-9 with pro-inflammatory cytokines, while in those with worse VA MMP-9 correlates with pro-angiogenic cytokines. Additionally, MMP- 9 levels are higher in the vitreous of non-diabetic controls than in the vitreous from PDR patients (P<0.0001, ROC: AUC= 0.7979 P<0.0001), regardless of VA.
Conclusions:
In-office vitreous sampling reveals MMP-9 levels in eyes with PDR to be higher in eyes with better VA. Vitreous levels of MMP-9 were highest in eyes of non-diabetic controls. In addition, evidence was found for activities of both pro-inflammatory and pro-angiogenic pathways in a manner that indicattes different roles for these important pathways in disease outcomes. This suggests a possible role for MMP-9 as a predictive biomarker of disease progression and severity as well as providing an enhanced understanding of the biochemical pathways involved in disease progression to provide the basis for improved disease management.
Keywords: 663 proteomics •
499 diabetic retinopathy •
490 cytokines/chemokines