Comprehensive analysis of vitreous chemokines involved in ischemic retinal vein occlusion

PURPOSE: To investigate vitreous levels of chemokines in eyes with ischemic retinal vein occlusion (RVO). METHODS: The vitreous humor was collected at the start of 23-gauge pars plana vitrectomy from patients with ischemic RVO and patients with idiopathic preretinal membranes (PRMs) and idiopathic macular holes (IMHs). The levels of 40 different chemokines were measured using magnetic color-bead-based multiplex assay. The chi-square test was performed for clinical variables such as sex, and the Mann–Whitney U test was performed to evaluate the differences in the chemokine levels between the RVO group and the control group. RESULTS: Vitreous humor was collected from 20 controls and 25 subjects with ischemic RVO. C-C motif ligand 17 (CCL17) was unmeasurable in more than 70% of the samples. The levels of 29 of 39 chemokines were statistically significantly elevated in the RVO group compared with the control group, including CCL21, C-X-C motif ligand (CXCL) 13, CCL27, CCL24, CX3CL1, CXCL6, interferon-gamma (IFN-γ), interleukin (IL) 1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-16, CXCL10, CXCL11, CCL8, CCL7, CCL13, CCL22, macrophage migration inhibitory factor (MIF), CXCL9, CCL3, CCL15, CCL20, CCL19, CCL23, CCL25, and tumor necrosis factor-alpha (TNF-α). Among the 29 elevated chemokines, we found that the levels of three chemokines (IL-8, CXCL9, and TNF-α) showed a more than six-fold increase in the RVO eyes versus controls, and CXCL9 expression showed the greatest change of all tested chemokines. CONCLUSIONS: Dozens of chemokines were found to be elevated in the vitreous of RVO eyes complicated with vitreous hemorrhage, suggesting that inflammation is severe in the ischemic retina. The knowledge of specific upregulation of chemokines in ischemic RVO could allow more targeted future therapies.