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(Investigative Ophthalmology and Visual Science. 2003;44:1945-1952.)
© 2003 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.02-0920
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Effects of Prostaglandin Analogues on Human Ciliary Muscle and Trabecular Meshwork Cells

Xiujun Zhao,1 Keri E. Pearson,2 Dietrich A. Stephan,2 and Paul Russell1

1From the Laboratory of Mechanisms of Ocular Diseases, National Eye Institute, National Institutes of Health, Bethesda, Maryland; and the 2Research Center for Genetic Medicine, Children’s National Medical Center, Washington, DC.

PURPOSE. To determine the effects of prostaglandin F2{alpha} analogues on gene expression of human ciliary muscle (HCM) and trabecular meshwork (HTM) cells.

METHODS. Cultures of HCM and HTM cells were established from five different donors treated for 9 days with 10 µg/mL of either latanoprost (free acid) or prostaglandin F2{alpha} ethanolamide and compared with control cells. The mRNA from the cells of the five individual donors was pooled and analyzed by using gene microarrays. Gene expression changes were confirmed by either real-time PCR or relative quantitative PCR.

RESULTS. Approximately 12 genes showed a twofold or greater change in expression under experimental conditions. Four of these may alter outflow. Aquaporin-1 and versican were downregulated in the HCM, whereas IGF1 and fibroleukin were upregulated in HTM. Expression levels of TNFSF10 and promelanosome-concentrating hormone also increased in the treated HTM cells. The mRNA levels for the prostaglandin FP receptor were downregulated in the ciliary muscle cells. Optineurin and {alpha}B-crystallin levels remained unchanged, but myocilin in the HTM cells was decreased in some samples.

CONCLUSIONS. Both analogues changed gene expression similarly in either HCM or HTM cells, but the changes appeared to be cell specific, perhaps indicating that other transcription factors are influential. Outflow of aqueous humor may be increased by the prostaglandin analogues by alterations in the extracellular matrix. Other changes may influence cellular metabolism, such as the increases in IGF1, tumor necrosis factor superfamily-10 and promelanosome-concentrating hormone.




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