Localization of thrombomodulin in the anterior segment of the human eye. Invest Ophthalmol Vis Sci.

Abstract

PURPOSE. To localize thrombomodulin (TM) in the anterior segment of the human eye. TM is a vascular endothelial cell surface glycoprotein that acts as a cofactor for the thrombin-catalyzed activation of the anticoagulant protease zymogen, protein C. METHODS. Immunohistochemical methods were used to detect TM expression in corneal epithelial cells, the lens epithelial cells, and other cells in the anterior segment of the eye. The expression of TM was also examined in cultured human corneal epithelial cells. RESULTS. TM was expressed in corneal epithelial cells, corneal endothelial cells, and nonpigmented ciliary epithelial cells, which are in direct contact with the aqueous humor. TM was also expressed in cultured corneal epithelial cells and showed cofactor activity. The amount of the antigen in the cultured corneal cells was approximately one tenth of that in human umbilical vein endothelial cells, but its specific cofactor activity (75%) was comparable to that of TM in human umbilical vein endothelial cells. The trabecular meshwork and endothelial cells lining Schlemm's canal also showed positive staining for TM. CONCLUSIONS. The TM in the cells that are in contact with the aqueous humor appears to be involved in maintaining the fluidity of the aqueous humor. In contrast, TM in cells that are not in contact with the aqueous humor may function in regulating cell proliferation and/or differentiation. (Invest Ophthalmol Vis Sci. 2000;41:3383-3390) T hrombomodulin (TM) acts as a cofactor for the thrombin-catalyzed activation of protein C and is present on the surface of vascular endothelial cells. 1,2 Activated protein C functions as an anticoagulant and operates by inactivating factors Va and VIIIa that are indispensable for the coagulation system. In addition, the binding of TM to thrombin inhibits fibrinogen clotting