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Arachidonic acid metabolism in human trabecular meshwork cells
R N Weinreb1, J R Polansky, J A Alvarado
1Department of Ophthalmology, University of California, San Diego, La Jolla 92093.
Investigative Ophthalmology & Visual Science
|November 1, 1988
Summary
Human trabecular meshwork (HTM) cells produce diverse prostaglandins and eicosanoids from arachidonic acid. These findings highlight novel pathways for eicosanoid synthesis in the eye's aqueous humor outflow system.
Area of Science:
- Ocular Physiology
- Biochemistry
- Cell Biology
Background:
- Prostaglandins and eicosanoids are crucial in the eye's aqueous humor outflow pathway.
- Understanding their production in trabecular meshwork is vital for physiological and pharmacological insights.
Purpose of the Study:
- To investigate eicosanoid production pathways in cultured human trabecular meshwork (HTM) cells.
- To identify specific cyclooxygenase and lipoxygenase products synthesized by HTM cells.
Main Methods:
- Utilized [14C]-arachidonic acid to trace metabolic pathways.
- Analyzed radiolabeled products using chromatography to identify prostaglandins and hydroxyeicosatetraenoic acids (HETEs).
- Assessed the effects of BW 755c and dexamethasone on lipoxygenase product biosynthesis.
Main Results:
- HTM cells primarily produced prostaglandin E2 (PGE2) and prostaglandin F2 alpha (PGF2 alpha) via cyclooxygenase.
- Significant amounts of 12- and 15-HETEs, along with leukotriene B4 (LTB4) and its metabolites, were identified as lipoxygenase products.
- BW 755c and dexamethasone demonstrated inhibitory effects on lipoxygenase pathways.
Conclusions:
- Human trabecular meshwork cells synthesize a broad spectrum of eicosanoids, including prostaglandins and lipoxygenase products.
- These findings expand the known biochemical capabilities of HTM cells and their potential role in regulating aqueous humor dynamics.