Purchase this article with an account.
H. Thieme, L. Choritz, R. Zorn, N.E. Bechrakis, R. Rosenthal, M.H. Foerster; Characterization Of Endothelin Receptors In Human Trabecular Meshwork Cells . Invest. Ophthalmol. Vis. Sci. 2004;45(13):4379.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Purpose: Endothelin is a potent vasoconstrictor and is probably involved in the pathogenesis of glaucoma. Its concentrations were found to be increased in plasma and aqueous humor of POAG–patients (for review: Pang et al.: Proc. Soc. Exp. Biol. Med. 215.21–34, 1997). However, there remains uncertainty whether endothelin is the cause of glaucoma or follows its development. The trabecular meshwork (TM) is considered a smooth muscle like tissue contributing to aqueous outflow regulation. Anti–endothelin effects on TM appear to be the modes of mechanisms for certain IOP pressure lowering drugs such as docosanoids (Thieme et al. IOVS, 42 (13), 3193–3201). This study was performed to characterize the endothelin receptors on human TM as well as the changes of tissue contractility in response to specific endothelin receptor antagonists. Methods: Measurements of isometric tension were performed using a force length transducer system. Isolated bovine TM and ciliary muscle (CM) strips were exposed to specific endothelin receptor antagonist. Western blot analysis of human TM cells were performed using specific antibodies against ET–A and ET–B receptors. The receptors were investigated on the mRNA level using PCR techniques. Results: Specific ET–A receptor antagonist BQ123 (10–6M) was able to inhibit endothelin–induced contractility in TM and CM (TM: 69.2 +/– 10.5% vs. 11.7 +/– 6.7%, n=7, p< 0.01; CM: 67.7 +/– 5.6% vs. 14.6 +/– 4.5%, n=6,p<0.01). BQ788, a specific ET–B receptor antagonist, had no effect in TM and only moderate effect in CM (TM: 69.2 +/– 15.5% vs. 66.4 +/– 8.9%, n=7,n.s.; CM: 67.7 +/– 5.6% vs. 48.1 +/– 4.3%, n=9, p<0,1). Western blot analysis revealed a clear signal for the ET–A receptor at 40 kDa in the human TM. No signal could be detected with the antibody against ET–B receptor. PCR results suggest mRNA for the ET–A receptor in the human TM cell cultures. Conclusions: According to a new concept of aqueous humor outflow regulation, TM relaxing substances appear to be ideal antiglaucomatous drugs leading to increased facility. From the data presented above we conclude that endothelin A receptor is present in the TM. Both from pharmacological as well as molecular biological studies this receptor turned out to be the most promising for intervention. Hypothetically, a specific ET–A receptor antagonist would lead to relaxation and hence increased outflow facility thus leading to lowered IOP. CR: none Support: Deutsche Forschungsgemeinschaft (DFG: Th 751/4–1)
This PDF is available to Subscribers Only