Role of chemokines in diabetic retinopathy

Summary We have detected altered expression of chemokines in the vitreous fluid of patients with proliferative diabetic retinopathy (PDR). In the early phase of disease chemokines (CXCL8, CCL2) are involved in leukocyte attraction. Later, CXCL12 may attract progenitor cells (endothelial cell precursors and fibrocytes) involved in establishment of neovessels and in formation of fibrovascular membranes. The myofibroblasts producing ECM in the fibrovascular membranes of the diabetic patients can originate from endothelial (precursor) cells via endoMT, from fibrocytes or from leukocyte‐like precursors. During the active disease stage also angiostatic chemokines (CXCL4, CXCL4L1 and CXCL10) are upregulated, probably in an attempt to counteract the stimulatory effects (angiogenesis and increased vascular permeability) of VEGF. Finally, CCL2 and CXCL10 have been reported to induce fibrosis and might play a role in the later stages of the pathology. Recently, we have demonstrated that CXCL4L1, a most potent angiostatic chemokine can be applied therapeutically as VEGF‐inhibitor in diabetic rats. Indeed, intraocular injections of CXCL4L1 early after the onset of diabetes protected animals against diabetes‐induced blood‐retinal barrier breakdown.