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W.E. Philipp, L.E. Speicher; Expression of CCN Family Proteins, CTGF, CYR61 and NOV in the Human Cornea . Invest. Ophthalmol. Vis. Sci. 2006;47(13):5041.
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Members of the CCN family of matricellular proteins are multifunctional growth factors representing a novel class of extracellular matrix–associated signalling molecules which are ligands of multiple integrin receptors. Several studies demonstrated that members of the CCN family are involved in the control of cell adhesion, chemotaxis, cell migration and cell proliferation. In particular, it was demonstrated that CTGF, CYR61 and NOV are potent angiogenic factors. In addition, CTGF was shown to possess strong fibrotic activity being involved in wound healing and several fibrotic diseases. The aim of the present study was to investigate whether CNN proteins are expressed in the normal cornea and whether their expression is increased in various corneal diseases.
20 inflamed and vascularized corneal buttons and 6 non inflamed corneas were obtained at the time of penetrating keratoplasty in patients with various corneal diseases. Immunohistochemistry was performed using the streptavidin–biotin–peroxidase method and highly specific antibodies against CTGF, CYR61 and NOV. 5 normal human corneas served as control.
In normal and non inflamed corneas CTGF and CYR61 were strongly expressed on epithelial cells and moderately on keratocytes and corneal endothelial cells while NOV was moderately expressed on epithelial cells. In addition, NOV and CTGF were also moderately expressed on endothelial cells of limbal vessels. In inflamed and vascularized corneas positive immunostaining of NOV and CTGF was also found in endothelial cells of of newly formed vessels in the stroma and the expression of CTGF and CYR61 was increased on keratocytes/fibroblasts particularly at sites of scar tissue or inflammation.
The results of the present study demonstrate that CTGF, CYR61 and NOV are expressed in normal corneas. The expression of these CCN proteins on vascular endothelial cells in diseased corneas strongly suggest an important role of these molecules in corneal neovascularization. Since immunostaining of CTGF and CYR61 was increased on keratocytes/fibroblasts in scar tissue, both molecules may be involved in tissue remodeling, scar formation and fibrosis.
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