Midterm response with latanoprost therapy in german ocular hypertension patients.

PURPOSE: The purpose of this prospective observational trial was to report the analysis of the midterm efficacy, safety, and discontinuation rates of a cohort of ocular hypertensive patients treated with latanoprost in Germany. METHODS: A subanalysis of patients with ocular hypertension who were previously treated on latanoprost monotherapy and continued within the study on this same medication for at least 6 months. RESULTS: 353 patients with ocular hypertension were included and treated with latanoprost monotherapy historically (1.4 +/- 1.3 years) and within the observational period of the study for a mean of 2.2 +/- 1.1 years. On latanoprost only, the average intraocular pressure at study entry was 18.4 +/- 2.7 mm Hg, and at 6 months the intraocular pressure was 18.3 +/- 2.3 mmHg (p = 0.54). During the observational period, the most common ocular side effect was conjunctival hyperemia (20.7%), and the most common systemic side effect was fatigue (3.1%). Nineteen patients (5.4%) discontinued latanoprost with the most common reason being insufficient efficacy (3.1%). Physician assessments of latanoprost monotherapy were "very good" to "excellent" for patient efficacy (75.2%), tolerability (83.8%), and patient satisfaction (82.1%). CONCLUSIONS: The study suggests that patients with ocular hypertension already treated with latanoprost monotherapy will continue to have, on average, at least midterm stable pressures, low incidence of side effects and discontinuations, as well as "very good" to "excellent" physician ratings of efficacy, tolerability, and patient satisfaction.

Proton-sensing G-protein-coupled receptors.

Blood pH is maintained in a narrow range around pH 7.4 mainly through regulation of respiration and renal acid extrusion. The molecular mechanisms involved in pH homeostasis are not completely understood. Here we show that ovarian cancer G-protein-coupled receptor 1 (OGR1), previously described as a receptor for sphingosylphosphorylcholine, acts as a proton-sensing receptor stimulating inositol phosphate formation. The receptor is inactive at pH 7.8, and fully activated at pH 6.8-site-directed mutagenesis shows that histidines at the extracellular surface are involved in pH sensing. We find that GPR4, a close relative of OGR1, also responds to pH changes, but elicits cyclic AMP formation. It is known that the skeleton participates in pH homeostasis as a buffering organ, and that osteoblasts respond to pH changes in the physiological range, but the pH-sensing mechanism operating in these cells was hitherto not known. We detect expression of OGR1 in osteosarcoma cells and primary human osteoblast precursors, and show that these cells exhibit strong pH-dependent inositol phosphate formation. Immunohistochemistry on rat tissue sections confirms the presence of OGR1 in osteoblasts and osteocytes. We propose that OGR1 and GPR4 are proton-sensing receptors involved in pH homeostasis.