Identification of chemokines and growth factors in proliferative diabetic retinopathy vitreous

Abstract

Associations were investigated between levels of chemokines and growth factors in the vitreous and proliferative diabetic retinopathy (PDR). Enrolled were 58 patients (58 eyes) requiring pars plana vitrectomy (PPV), with PDR (n=32, none with traction retinal detachment) or not (non-PDR). In the latter, 16 had macular hole (MH) and 10 had epiretinal membrane (ERM). With a multiplex bead immunoassay, levels of 11 chemokines and growth factors were measured from the undiluted vitreous sample from each patient. In the non-PDR eyes, the levels of the 11 chemokines and growth factors tested were similar between patients with MH and those with ERM. However, the levels of all 11 were significantly higher in the PDR eyes relative to the non-PDR; CCL17, CCL19, and TGFβ3 were markedly upregulated and have not been investigated in PDR previously. The significantly higher levels of CCL4 and CCL11 in PDR contradict the results of previous reports. Based on Spearman's nonparametric test, moderate-to-strong correlations were found between VEGF and other mediators. Our results indicate that these chemokines and growth factors could be candidates for research into targeted therapies applied either singly or in combination with anti-VEGF drugs for the treatment of PDR.

Figure 1

Scatter plots of chemokines and growth factors levels in PDR vitreous. By multiplex beads immunoassay, significant elevation of all 11 mediators was found in PDR vitreous as compared with controls. Sixteen MH and 10 ERM patients constituted the non-PDR group. Among 11 mediators, CCL17, CCL19, and TGFβ3 were identified to be associated with PDR firstly. The vertical bars represent median with range.

Figure 2

Correction analysis between VEGF and other mediators in PDR vitreous. Based on Spearman's analysis, moderate-to-strong corrections were observed between VEGF and CCL2, CCL11, CCL17, CCL19, CXCL9, TGFβ1, TGFβ2, and TGFβ3.