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      Endothelin-like immunoreactivity in aqueous humor of patients with primary open-angle glaucoma and cataract.

      Graefe's Archive for Clinical and Experimental Ophthalmology
      Administration, Topical, Adrenergic beta-Antagonists, administration & dosage, therapeutic use, Aqueous Humor, metabolism, Cataract, Cataract Extraction, Endothelin-1, drug effects, Glaucoma, Open-Angle, drug therapy, surgery, Humans, Intraocular Pressure, physiology, Ophthalmic Solutions, Radioimmunoassay

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          Abstract

          Experimental evidence suggests a role of endothelin-1 (ET) in the regulation of intraocular pressure (IOP). Therefore, in patients undergoing cataract surgery, ET-like immunoreactivity (ETIR) was measured by radioimmunoassay in pooled samples of aqueous humor of eyes with primary open-angle glaucoma (POAG) and normotensive eyes with cataract only. ETIR was significantly (P < 0.05) higher in patients with cataract and POAG (20.5 +/- 1.8 pg/ml, n = 12; preoperative IOP 21.4 +/- 1.1 mmHg, n = 33) than in patients with cataract only (15.8 +/- 1.6 pg/ml, n = 15; preoperative IOP 16.0 +/- 0.6 mmHg, n = 77). This finding may indicate a role of ET in POAG or ocular antihypertensive treatment, and its relevance should be further investigated.

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          Endothelin-1 plasma levels in normal-tension glaucoma: abnormal response to postural changes.

          Endothelin-1 (ET-1) is a potent vasoconstrictor peptide produced by vascular endothelial cells. ET-1 may have a role in the pathogenesis of various vascular diseases. There are reports in the literature that ET-1 plasma levels are raised in normal-tension glaucoma (NTG) patients. ET-1 concentration, plasma renin activity, and 24-h blood pressure were measured in 21 high-tension glaucoma (HTG) patients, 19 NTG patients, and 20 non-glaucomatous controls in supine and upright positions. ET-1 plasma levels tended to be higher in NTG patients (3.2 +/- 2.2 pg/ml) than in HTG patients (2.2 +/- 0.6 pg/ml) and controls (2.6 +/- 0.7 pg/ml). The differences, however, were not statistically significant. The individual scatter was significantly greater in the NTG group, indicating that our NTG patients are a heterogeneous population. The physiological increase in ET-1 plasma level after changing from the supine to the upright position was absent in NTG patients. Plasma renin activities tended to be lower in NTG patients (1.2 +/- 1.2 ng/ml/h) than in HTG patients (1.3 +/- 0.8 ng/ml/h) and controls (2.0 +/- 1.7 ng/ml/h). This may explain why NTG patients had relatively low blood pressure despite high ET-1 levels. Our data support the hypothesis that vascular dysfunction may be involved in the pathogenesis of optic nerve damage in normal-tension glaucoma.
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            Endothelin-like immunoreactivity in the aqueous humour and in conditioned medium from cultured ciliary epithelial cells.

            Endothelin-like immunoreactivity was detected in human (15.6 +/- 2.7 pg/ml) and bovine (11.1 +/- 0.98 pg/ml) aqueous humour of the eye. These concentrations are 2-3 times higher than the corresponding plasma levels. Cultured human nonpigmented ciliary epithelial cells released endothelin-like immunoreactivity with a maximum of 2.1 +/- 0.32 pg/(cm2* 48 h). The release was stimulated by fetal calf serum, thrombin, carbachol and phorbol ester and blocked by cycloheximide. Immunocytochemistry showed cytoplasmic staining of cultured human nonpigmented ciliary epithelial cells for endothelin-1. Endothelin-1 was shown to induce contractions in isolated human ciliary muscle by isometric force measurements. Endothelin in the aqueous humour may play a role in the regulation of intraocular pressure.
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              Endothelin-evoked contractions in bovine ciliary muscle and trabecular meshwork: interaction with calcium, nifedipine and nickel.

              In the present study, we compared contractile responses of isolated bovine ciliary muscle and trabecular meshwork strips to endothelin-1 and carbachol. 1. Endothelin-1 is a potent contracting agent for ciliary muscle and trabecular meshwork. The EC50 was 5 x 10(-9) mol/l for both tissues. The maximal force evoked by endothelin was 73% of the maximal carbachol response in trabecular meshwork and 52% in ciliary muscle. 2. Carbachol contracted both tissues with an EC50 of 2 x 10(-7) mol/l. 3. In ciliary muscle, the tension was completely dependent on extracellular calcium. 4. In trabecular meshwork, 23 +/- 4% of the endothelin- and 42 +/- 10% of the carbachol-induced force response remained after removal of extracellular calcium. 5. Nifedipine (10(-5) mol/l) had only a slight relaxing effect in both tissues. 6. Nickel (10(3) mol/l) inhibited the development of force in both tissues. The relaxation induced by nickel was more pronounced in endothelin- than in carbachol-induced contractions. Different intracellular mechanisms mediating the action of endothelin and carbachol can be described: i) a calcium- and a nickel-sensitive pathway in both tissues and ii) an additional mechanism independent of external calcium in trabecular meshwork. These results indicate functional differences between the contractile region of trabecular meshwork and ciliary muscle. Endothelin may participate in accommodation and regulation of the intraocular pressure.
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