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K. G. Howell, K. A. Cook, M. P. Fautsch; Characterization of Differentially Expressed Genes in Latanoprost Treated Primary Human Trabecular Meshwork Cells. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1618.
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Prostaglandin therapy has been known to lower intraocular pressure in normal and glaucomatous eyes through the uveoscleral pathway. Recently, latanoprost, an isopropyl ester analogue of prostaglandin F2-alpha, has been shown to increase outflow facility through the trabecular meshwork pathway. We examined the effect of latanoprost on primary human trabecular meshwork cells to identify differentially expressed genes.
Three independent confluent primary human trabecular meshwork cell lines were incubated with Dulbecco’s Modified Eagle’s Media with and without latanoprost-free acid (100 nM; added daily). Following 24-hour and 72-hour incubations, total RNA was isolated from each cell line. Total RNA (100 ng) was amplified, processed into cRNA, and used to probe Affymetrix GeneChip Human Genome U133 Plus 2.0 arrays. Microarray data was analyzed using Partek (Partek, Inc.) and MetaCore (Genego, Inc.) software programs. Genes with at least a 1.5-fold change in expression were used in the analysis.
Primary trabecular cells treated with latanoprost-free acid showed significant changes in gene expression. Within 24 hours of treatment, approximately 2000 genes were differentially expressed. Of these, 137 genes maintained differential expression at 72 hours. Genes involved in cellular processes associated with the extracellular matrix (hyaluronan synthase), integrin signaling (integrin, alpha 8), cell adhesion (melanoma cell adhesion molecule), cytoskeletal remodeling (filamin A), and gene transcription (c-jun) were affected.
Latanoprost treated human trabecular cells produce a unique molecular profile that differs from cells cultured in media alone. Further analysis of these pathways may lead to new ideas regarding how pressure lowering drugs such as latanaprost affects trabecular cell function.
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