Role of angiogenenic and angiostatic chemokines in the formation of choroidal neovascular membranes

Abstract

Abstract: : Purpose: Angiogenesis is controlled by a complex interaction of molecules including chemokines that can promote (angiogenic) or inhibit (angiostatic) growth. We studied the role of chemokines and their receptors in the formation of choroidal neovascular membranes (CNVM). Methods: CNVM were surgically removed from patients with age–related macular degeneration (AMD) and for comparison vitreo–retinal membranes from patients with proliferative diabetic retinopathy (PDR). Paraffin embedded sections were stained with antibodies against angiogenic chemokines CXCL1, CXCL2, CXCL8 and angiostatic chemokines CXCL9, CXCL10, and chemokine receptors CXCR1, CXCR2, and CXCR3. To identify the cell types present sections were also stained with CD3, CD4, CD8, and CD68. Protein levels of chemokines, cytokines, and growth factors in paired vitreous samples were measured by the Luminex bead assay. Results: CNVM from patients with AMD stained positive for CXCL8, CXCL9, and CXCL10 with most staining around vascular structures. AMD CNVM were positive for all three chemokine receptors with CXCR1 and CXCR3 most strongly expressed. CNVM from patients with PDR were negative for all three chemokines, except for staining on infiltrating cells. At the protein level, CCL2 was present in vitreous samples from both groups of patients, but was the only molecule of those tested found in AMD samples. By comparison, IL–6, CXCL8, and VEGF were found in PDR samples. Conclusions:These data support a role for chemokines in the growth of CNVM. The differences between chemokine expression in AMD and PDR membranes and vitreous composition reflects the different cellular nature and site of the two tissues The interaction of angiogenic versus angiostatic chemokines and their induction appear important in CNVM formation.

Keywords: cytokines/chemokines • choroid: neovascularization • immunohistochemistry