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Editors Selection IGR 11-4
Basic research: TM, MMP and Latanoprost
Comment by James Lindsey on:
14039 Effect of latanoprost on the expression of matrix metalloproteinases and their tissue inhibitors in human trabecular meshwork cells, Oh DJ; Martin JL; Williams AJ et al., Investigative Ophthalmology and Visual Science, 2006; 47: 3887-3895
Recent evidence indicates signal transduction events are triggered in trabecular meshwork (TM) cells exposed to intraocular pressure-lowering analogues of prostaglandin F2α . This raises the possibility that these analogues may alter the metabolism of TM extracellular matrix. Hence, Oh et al. (642)surveyed the expression of mRNAs for 12 matrix metalloproteinases (MMPs) and all four tissue inhibitors of matrix metalloproteinases (TIMPs) in cultured human TM cells following exposure to physiologic or supraphysiologic latanoprost acid concentrations for 24 hours. Each mRNA type was assayed in TM cell lines generated from five different donors. Gene expression was determined using reverse transcriptase real time PCR assays.
Vehicle-treated control cultures expressed mRNA for a number of MMPs that could potentially target TM extracellular matrix components. Also expressed were mRNAs for each of the four TIMP types.Latanoprost acid treatment induced variable alterations of MMP mRNA among the TM cell lines examined. Increases were seen in a majority of the cell lines for five of the MMP mRNA types.
Latanoprost acid treatment induced variable alterations of MMP mRNA among the TM cell lines examinedHowever, increases were seen in a majority of the cell lines for all of the TIMP mRNA types. The authors conclude these results are consistent with the view that latanoprost does not shift TM gene transcription towards extracellular matrix reduction.
The experiments appear to have been done carefully with appropriate controls. However, the authors acknowledge that only one time point was examined. Hence, gene expression may have been different either earlier or later than 24 hours after treatment initiation. Other limitations are that MMP protein secretion, MMP activity in the culture medium, as well as the biosynthesis and assembly of extracellular matrix components were not measured. Thus, further work is needed to clarify the significance of these results for TM extracellular matrix metabolism.
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