Effects of prostaglandin analogues on human ciliary muscle and trabecular meshwork cells.
OBJECTIVE
To determine the effects of prostaglandin F(2alpha) 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 microg/mL of either latanoprost (free acid) or prostaglandin F(2alpha) 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 alphaB-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.
Zhao
Xiujun
X
Laboratory of Mechanisms of Ocular Diseases, National Eye Institute, National Institutes of Health, Bethesda, Maryland, USA.
Pearson
Keri E
KE
Stephan
Dietrich A
DA
Russell
Paul
P
D000199:Actins / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000959:Antihypertensive Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D002924:Ciliary Body / Q000187:drug effects* / Q000378:metabolism; D003893:Desmin / Q000378:metabolism; D015232:Dinoprostone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D005136:Eye Proteins / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D005786:Gene Expression Regulation; D006801:Humans; D000077338:Latanoprost; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011461:Prostaglandins F, Synthetic / Q000494:pharmacology*; D012313:RNA / Q000302:isolation & purification; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014129:Trabecular Meshwork / Q000187:drug effects* / Q000378:metabolism
D000199:Actins; D000959:Antihypertensive Agents; D003893:Desmin; D005136:Eye Proteins; D011461:Prostaglandins F, Synthetic; D012333:RNA, Messenger; C107684:prostaglandin E2 ethanolamide; D012313:RNA; D000077338:Latanoprost; D015232:Dinoprostone