Involvement of the Chemokine SDF–1 and Its Receptor CXCR4 in Corneal Angiogenesis

Abstract

Abstract: : Purpose: The aim of the study was to investigate whether cultured human corneal fibroblasts and myofibroblasts express chemokine CXCR4 receptors on their cell surface and to determine the presence of its specific ligand, SDF–1. We also investigate the balance between angiogenic factors (VEGF, CXCR4) and PEDF in normal and vascularized human corneas. Methods: Human corneal fibroblast and myofibroblast cultures were obtained using human donor corneas. Cells were immunostained using specific antibodies against SDF–1, CXCR4, alpha smooth muscle actin, and analyzed with a confocal microscope. Twenty vascularized corneal buttons were obtained at the time of penetrating keratoplasty in patients with various corneal diseases (i.e. graft rejection, herpetic keratitis). VEGF, PEDF and CXCR4 expressions were detected by Western–blot analysis and compared to normal corneas. Results: CXCR4 is similarly expressed in cultured corneal fibroblasts and myofibroblasts. SDF–1 is not expressed in corneal fibroblasts but strongly expressed in activated myofibroblasts. Western–blot analysis detected the presence of PEDF and CXCR4 in normal corneas in which VEGF is weakly expressed. Conversely, we observed a lower expression of PEDF whereas CXCR4 and VEGF were increased in vascularized corneas. Conclusions: These results indicate that both SDF–1 and CXCR4 are involved in the development of corneal angiogenesis.

Keywords: neovascularization • cytokines/chemokines • cornea: stroma and keratocytes