Abstract
Purpose: :
The focus of this study was to explore potential proteomic biomarkers in vitreous samples of patients with different severities of proliferative diabetic retinopathy (PDR).
Methods: :
Seventy-two in-office vitreous aspirates were obtained from 42 patients with PDR directly preceding intra-vitreal injection of bevacizumab. Twenty-four age matched controls had vitreous aspirations drawn prior to vitrectomy for macular hole or retinal detachment surgery. All vitreous aspirates in this study, were drawn using a pars plana approach, with a 25 gauge needle on a 1 mL syringe. Approximately 0.05 to 0.10 mL of vitreous fluid was aspirated from the mid-vitreous cavity. All 96 samples were probed against 44 pathway proteins using Reverse Phase Protein Microarray technology.
Results: :
Statistical analysis revealed 17 proteins that have significantly different levels of abundance between the non-diabetic controls and PDR samples. The proteins that change most significantly are: C3a, αB Crystallin, MMP-9 and COX2, all of which have a P-value of <0.01 and significant ROC curves with an AUC >0.80. Interestingly, when the PDR patients were split based on patients with best corrected ETDRS VA of 20/200 or less versus patients withVA better than 20/200, 20 proteins were shown to have significantly different levels. The presence of vitreous hemorrhage did not change the results of the biomarkers studied. The most significant of these proteins was FGFR Tyr 653/654, Estrogen Receptor α Ser118, MMP-9 and BCL2 Thr 56, all of which have P-values <0.01 and significant ROC curves with an AUC > 0.80.
Conclusions: :
Proteomic analysis reveals that there are biomarkers significantly different between diabetic and non-diabetic patients. In addition, biomarkers differ between diabetic patients who have significant loss in vision versus those with stable vision. These differences in protein expression levels may lead to the discovery of biomarkers that may provide us with better understanding of the biology of PDR and possibly aid in the development of future treatments to prevent the progression of PDR.
Keywords: proteomics • diabetic retinopathy • proliferation