Expression of tissue plasminogen activator during eye development

Abstract

Tissue plasminogen activator (tPA) is a serine protease responsible for the activation of plasminogen to plasmin as well as extracellular matrix remodeling. While tPA is used clinically to treat some retinal disorders and it is expressed at low levels in the adult eye, its expression pattern during eye development had never been determined. tPA protein is broadly dispersed in the lens placode and optic vesicle of the mouse eye and it becomes highly localized to the apical surfaces of both the lens pit and the optic cup as they invaginate. In the lens, tPA remains at the apical tips of both lens epithelial and fiber cells from the lens vesicle stage until birth in the mouse, when it begins to downregulate to barely detectable levels in adults. In humans, tPA is found in a similar pattern in the lens vesicle and early lens, however, appreciable protein is also detected in the cytoplasm of lens epithelial cells until adulthood. In the retina, tPA is found at the apical interface between the developing retinal pigmented epithelium and neural retina, then begins to downregulate once the photoreceptors have differentiated. In conclusion, tPA protein is found in a different pattern in embryonic versus adult eyes and may be involved in remodeling of the extracellular environment during eye development.