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104. Jahrestagung der Deutschen Ophthalmologischen Gesellschaft 2006
Abstract
Abstract
SA.17.05 The fast and the slow mechanisms of action of prostaglanine analogues – uveoscleral versus trabecular action Thieme H.1, Choritz L.1, Rosenthal R.2, Pfeiffer N.1
1Universitäts-Augenklinik, Johannes Gutenberg-Universität, Mainz; 2Institut für Klinische Physiologie,Charité Universitätsmedizin, Klinikum Benjamin Franklin, Berlin Objective: The IOP lowering effect of prostaglandine analogues is believed to act via enhancement of uveoscleral flow. Here they activate c-fos and MMPs which in turn leads to collagen degradation. This, however, takes time. Contrary to this the IOP lowering effects are very rapid, usually within 8-12 hours. Additionally the IOP increases rapidly after the drugs are discarded. This stuy clarifies the influence of prostaglandine analogues on the conventional outflow (trabecular meshwork).
Methods: Isometric tension measurements of single trabecular meshwork strips were performed using carbachol and endothelin as contracting compounds. Intracellular calcium measurements using fura-2 were performed as well as western blot analysis of human trabecular meshwork cells.
Results: Prostaglanine analogues such as PGF-2 alpha and Fluoprostenol are able to inhibit the endothelin induced contraction in trabecular meshwork strips (reduction of 30% (PGF 2 alpha) and 36% (Fluoprostenol)). Both receptors for prostaglandine and endothelin could be detected with protein blotting methods. Calcium measurements were in line with contractility measuremtns where endothelin induced contraction resulted in a calcium rise intracellularily and relaxation in the opposite effect (reduction by 57% for PGF 2 alpha).
Conclusions: A relaxation of the trabecular meshwork (or an endothelin inhibitory effect) suggests to lower intraocular pressure. Such an inhibition results after administration of prostaglandine analogues. We postulate from these data that additionally to the slow acting efects via the uveoskleral outflow a relatively fast effect via the meshwork exists. These data explain the fast effects of prostglandine analogues observed clinically. Our understanding about the mode of action of prostglandine analogues therefore needs to be revised.
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