Purchase this article with an account.
David F. Woodward, Jenny W. Wang, David Piwnica, W D. Stamer; Rapid Characterization Of Functional Prostanoid Receptor Pharmacology In Human Ocular Anterior Segment Cells By Cellular Dielectric Spectroscopy. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2071.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
: A complete and singular pharmacological analysis of functional prostanoid receptor expression in multiple ocular cell types has not been previously achieved. By employing cellular dielectric spectroscopy, such a comprehensive and rapid pharmacological analysis was achieved.
Primary human ocular cells were studied in a 96-well format using cellular dielectric spectroscopy. In brief, cellular dielectric spectroscopy measures cellular impedance to an electric current that flows over and between cells. Drugs were evaluated over a 10-12 - 10-5M dose range.
In human ciliary smooth muscle cells (CSM), which are the target cell for anti-glaucoma drugs that increase uveoscleral outflow, functional EP2 and FP receptors were clearly identified. Although PGD2 stimulated CSM cells, it appeared to stimulate DP2 receptors. EP3 and EP4 appeared weakly coupled in CSM cells . In marked contrast, both IP and TP receptor stimulation were very potent with E.C.50 values similar to those produced by FP agonists. In trabecular meshwork (TM) cells, only FP and EP3 receptor stimulation resulted in consistent and potent activation. In endothelial cells of Schlemm’s canal (ECSC), functional evidence for DP2, EP2, EP4, FP, IP and TP receptors was obtained. Human iris sphincter muscle (ISM) cells functionally expressed EP3, IP, TP and surprisingly FP receptors. The profile was quite different non-pigmented epithelial (NPE) cells: here no evidence for functional FP receptors was obtained, whereas EP2, EP4, IP and TP receptor agonists potently stimulated NPE cells. In all instances TP receptor activation produced an opposite CDS signature response compared to other prostanoid receptors.
The distribution of prostanoid receptors in human ocular cells is widespread, as previously suggested by immunohistochemical analyses. The physiological and pathophysiological significance of DP2, IP and TP receptors requires more detailed studies.
This PDF is available to Subscribers Only