ABSTRACT
BACKGROUND: The pathophysiological mechanisms of macular edema secondary to branch retinal vein occlusion (BRVO) remain unclear. OBJECTIVES: To analyze the protein profile of human vitreous of patients with BRVO and to identify specific dysregulated proteins. MATERIALS AND METHODS: Undiluted vitreous humor samples from patients with treatment naïve BRVO and 15 controls with idiopathic floaters were analyzed in this clinical-experimental study using capillary electrophoresis coupled to a mass spectrometer (CE-MS) and tandem mass spectrometry (MS/MS). Quantitative analysis of the dysregulated proteins was performed with enzyme-linked immunosorbent assay (ELISA). Protein-protein interactions were depicted with the STRING database. RESULTS: A total of 84 proteins were found in the human vitreous samples of 15 patients with BRVO and 15 controls. In all, 14 proteins were significant when comparing the signal intensities of BRVO and control samples. Six significant dysregulated proteins with p < 0.001 were further verified with ELISA. Clusterin, complement factor C3, prostaglandin-H2 Disomerase and vitronectin were significantly upregulated in the BRVO group and opticin was downregulated. The protein interactions analysis showed associations with inflammatory cascades, matrix changes, mechanisms of cell survival und death. CONCLUSIONS: The results of the study reveal that the proteomic composition of vitreous humor differed significantly between the patients with BRVO and the controls. Whether the identified proteins may serve as potential biomarkers for pathophysiology, diagnostics or therapy should be examine in further studies.
Subject(s)
Macular Edema , Retinal Vein Occlusion , Humans , Proteome , Proteomics , Tandem Mass Spectrometry , Vascular Endothelial Growth Factor A , Vitreous BodyABSTRACT
PURPOSE: To correlate key inflammatory and pro-angiogenic cytokines from undiluted vitreous fluid of treatment-naïve patients with central retinal vein occlusion (CRVO) with SD-OCT parameters. METHODS: Thirty-five patients (age 71.1 years, 24 phakic, 30 non-ischaemic) underwent intravitreal combination therapy, including single-site 23-gauge core vitrectomy. Twenty-eight samples from patients with idiopathic, non-uveitis floaterectomy served as controls. Levels of interleukin 6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and vascular endothelial growth factor (VEGF-A) were correlated with visual acuity (logMar), category of CRVO (ischaemic or non-ischaemic) and morphological parameters, such as central macular thickness (CMT), thickness of neurosensory retina (Tneuro), extent of serous retinal detachment (SRT) and disintegrity of the IS/OS and others. RESULTS: Mean IL-6 was 64.7 pg/ml (SD ± 115.8), mean MCP-1 1015.7 pg/ml (± 970.1), and mean VEGF-A 278.4 pg/ml (± 512.8), which was significantly higher than the control values of IL-6 6.2 ± 3.4 pg/ml (p = 0.06), MCP-1 253.2 ± 73.5 pg/ml (p < 0.0â000â001) and VEGF-A 7.0 ± 4.9 pg/ml (p < 0.0006), respectively. All cytokines correlated highly with one another (correlation coefficient r = 0.82 for IL-6 and MCP-1; r = 0.68 for Il-6 and VEGF-A; r = 0.64 for MCP-1 and VEGF-A). IL-6 correlated significantly with CMT, TRT, SRT, dIS/OS, and dELM. MCP-1 correlated significantly with SRT, dIS/OS, and dELM. VEGF-A did not correlate with changes in SD-OCT, while it had a trend to be higher in the ischaemic versus the non-ischaemic CRVO groups (p = 0.09). CONCLUSIONS: The inflammatory cytokines were more often correlated with morphological changes assessed by SD-OCT, whereas VEGF-A did not correlate with CRVO-associated changes in SD-OCT. VEGF inhibition alone may not be sufficient to decrease the inflammatory response in CRVO therapy.
