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W.E. Philipp, L. Speicher; Expression of Angiostatin and Endostatin in Normal and Vascularized Human Corneas . Invest. Ophthalmol. Vis. Sci. 2003;44(13):825.
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Purpose: It is believed that a balance between angiogenic and anti-angiogenic factors is responsible for the avascularity of the normal cornea. Angiostatin and endostatin are potent angiogenesis inhibitors which are proteolytic fragments of plasminogen and collagen XVIII, respectively. Since the switch to corneal neovascularization probably requires both upregulation of angiogenic stimulators and downregulation of angiogenic inhibitors we investigated the expression of angiostatin and endostatin in normal and vascularized human corneas to shed more light on the pathogenesis of corneal neovascularization. Methods: 24 vascularized human corneal buttons were obtained at the time of penetrating keratoplasty in patients with various corneal diseases. Immunohistochemistry was performed on frozen sections using the streptavidin-biotin-peroxidase method and antibodies against angiostatin, endostatin and against von Willebrand's factor to confirm the presence of neovascularization. 5 normal human corneas served as control. Results: In normal corneas angiostatin was strongly expressed particularly by basal epithelial cells while endostatin was strongly expressed in the whole epithelium, by the epithelial basement membrane, by layers of Descemet's membrane and by cells of the trabecular meshwork. In inflamed and vascularized corneas positive immunostaining of angiostatin and endostatin was also found in endothelial cells and the basement membrane of newly formed vessels in the stroma and on keratocytes/fibroblasts in the stroma. Conclusions: The results of the present study strongly suggest that angiostatin and endostatin may be involved in the maintenance of the avascularity of the normal cornea. Since both angiogenesis inhibitors are strongly expressed in inflamed and vascularized corneas both molecules may also play an important role in antagonizing overwhelming effects of angiogenic factors like VEGF during corneal neovascularization.
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