Human Trabecular Meshwork Cells
In man, most of the aqueous humor drainage and the major resistance to outflow occur across the trabecular meshwork and inner wall of Schlemm’s canal. Pros-taglandins are known to alter intraocular presure (IOP) and have been implicated in both physiological and pathophysiological aspects of IOP regulation. In the present study, we have characterized pathways of arachidonic acid metabolism in human trabecular meshwork (HTM) cells and measured basal and hormone-stimulated PGE2 release. The principal product of [1-14C]PGH2 metabolism and [1 − 14C]arachidonic acid metabolism was PGE2. Immunoreactive PGE2 was released in excess of immunoreactive 6-keto-PGF1α during 15-min incubations in phosphate-buffered saline. Incubation wth indomethacin (5 μM) for 20 min substantially reduced (80–85% inhibition) PGE2 formation from AA. Overnight incubation with dexamethasone (ID50 = 3.3 × 10−9M) inhibited basal and A23187-stimulated PGE2 release. The effects of dexamethasone on PGE2 synthesis and release could be prevented by pretreatment of the HTM cells with 2 μg/ml cyclo-heximide. A23187 (10−6-10−5 M) elicited a significant P <0.05 compared to control) increase in PGE2 release (RIA determinations).
KeywordsTrabecular Meshwork Arachidonic Acid Metabolism PGE2 Synthesis Primary Open Angle Glaucoma PGE2 Release
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- Camras, C.B., Bito, L.Z., and Eakins, K.E., 1979, Reduction of intraocular pressure by prostaglandins applied topically to the eyes of conscious rabbits, Invest. Ophthalmol. Vis. Sci. 16:1125–1134.Google Scholar
- Miller, J.D., Eakins, K.E., and Atwal, M., 1973, The release of PGE2-like activity into aqueous humor after paracentesis and its prevention by aspirin, Invest. Ophthalmol. Vis. Sci. 12:939–942.Google Scholar
- Peyman, K., Peyman, G.A., McGetrick, J., and Janevicius, R., 1979, Indomethacin inhibition of prostaglandin-mediated inflammation following intraocular surgery, Invest. Ophthalmol. Vis. Sci. 16:760–762.Google Scholar
- Polansky, J. R., Gospodarowicz, D., Weinreb, R., and Alvarado, J., 1978, Human trabecular meshwork cell culture and glycosaminoglycan synthesis, Invest. Ophthalmol. Vis. Sci. 17(ARVO Suppl.):207.Google Scholar
- Schachtschabel, D.O., Rohen, J.W., Waver, J., and Sames, K., 1982, Synthesis and composition of glycosaminoglycans by cultured human trabecular meshwork cells, Albrecht von Graefes Arch. Klin. Exp. Ophthalmol. 218:113–117.Google Scholar
- Segawa, K., 1975, Ultrastructural changes of the trabecular tissue in primary open angle glaucoma, Jpn. J. Ophthalmol. 19:317.Google Scholar
- Southren, A.L., Gordon, G.G., Munnangi, P.R., Vittek, J., Schwartz, J., Monder, C, Dunn, M.W., and Weinstein, B.I., 1983, Altered cortisol metabolism on cells cultured from trabecular meshwork specimens obtained from patients with primary open-angle glaucoma, Invest. Ophthalmol. Vis. Sci. 24:1413–1417.PubMedGoogle Scholar
- Southren, A. L., l’Hommedieu, D., Ravikumar, S., Gordon, G. G., Dunn, M. W., and Weinstein, B. I., 1984, Potentiation of the ocular hypertensive effect of dexamethasone by 5ß-dihydrocortisol, Invest. Ophthalmol. Vis. Sci. 25 (ARVO Suppl.):304.Google Scholar
- Worthen, D.M., and Cleveland, P.H., 1982, Fibronectin production by cultured human trabecular meshwork cells, Invest. Ophthalmol. Vis. Sci. 22:265–269.Google Scholar