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W.E. Philipp, L. Speicher; Expression of METH–1, METH–2 and Pigment Epithelium–Derived Factor in Human Corneas . Invest. Ophthalmol. Vis. Sci. 2004;45(13):4814.
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Purpose: It is assumed that groups of specific angiogenic and anti–angiogenic factors are involved in the regulation of vascular networks and that a balance between these factors is responsible for the avascularity of the normal cornea. METH–1 and METH–2 represent a new family of anti–angiogenic proteins with metalloprotease,disintegrin, and thrombospondin domains and are suggested to be about 20–fold more potent than thrombospondin–1. Pigment epithelium–derived factor (PEDF) a neurotrophic serpin was recently shown to be a potent inhibitor of angiogenesis. The aim of the present study was to compare the expression of anti–angiogenic factors METH–1, METH–2 and PEDF in normal and vascularized human corneas. Methods: 5 normal human corneas with a scleral rim and 20 inflamed and vascularized corneal buttons 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 METH–1, METH–2 and PEDF. Results: In normal corneas both, METH–2 and PEDF were strongly expressed by epithelial and corneal endothelial cells while only weak positive immunostaining of METH–1 was found in some epithelial cells. In diseased corneas increased expression of METH–2 and PEDF was found in the stroma particularly at sites with scar tissue. Conclusions: The results of the present study clearly show that in contrast to METH–1, METH–2 and PEDF are strongly expressed in normal corneas and thus may be involved in the maintenance of the avascularity of the normal cornea. Furthermore, the increased expression of METH–2 and PEDF in diseased corneas strongly suggests that both anti–angiogenic factors may be involved in the regulation and control of corneal neovascularization.
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