Abstract
Purpose::
Ephrins are cell-surface associated ligands of the largest known subfamily of tyrosine kinases, called the Eph family of receptors. These ligands and their Eph receptors have initially been shown to play an important role during development particularly of the neuronal system. However, an increasing body of evidence suggests that these multifunctional molecules are essential mediators of angiogenesis of similar importance like VEGF and angiopoietins. Furthermore, these new molecules are involved in tumor growth, cell adhesion and cell trafficking. The aim of the present study was to investigate and to compare the expression of ephrins A1, A2, A3, A4 and A5 in normal, inflamed and vascularized human corneas.
Methods::
Immunohistochemistry was performed using the streptavidin-biotin-peroxidase method and highly specific antibodies against ephrins A1, A2, A3, A4 and A5 in 5 normal, human corneas with a scleral rim from human donor eyes and in 21 inflamed and vascularized human corneas obtained at the time of penetrating keratoplasty in patients with various corneal diseases.
Results::
In normal corneas the investigated ephrins were strongly expressed on corneal epithelial cells with ephrin A2 showing the strongest staining. Moderate staining of all ephrins investigated in this study was also found on endothelial cells of limbal vessels, while keratocyte staining was only week for these molecules. In addition, moderate staining of ephrin A3 was also found on corneal endothelial cells. In inflamed and vascularized human corneas increased ephrin A1, A2, A3, A4 and A5 expression was found on vascular endothelial cells of newly formed vessels in the stroma, and staining of Ephrin A2, A3, A4 and A5 was increased on fibroblasts in scar tissue.
Conclusions::
The results of the present study show that ephrins A1,A2,A3,A4 and A5 are expressed in normal corneas particularly on epithelial cells. The increased expression of these molecules on vascular endothelial cells of new vessels in the stroma and on fibroblasts in scar tissue strongly suggest that these molecules may be involved in angiogenesis and possibly in scar formation in various corneal diseases.
Keywords: cornea: basic science • neovascularization • immunohistochemistry