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Editors Selection IGR 13-3
Basic research: Myocilin
Comment by Michael Fautsch on:
13752 First look at the effect of overexpression of TIGR/MYOC on the transcriptome of the human trabecular meshwork, Borras T; Bryant PA; Chisolm SS, Experimental Eye Research, 2006; 82: 1002-1010
The function of myocilin and its functional association with glaucoma have remained elusive, despite considerable research effort. The presence of myocilin in human trabecular meshwork cells has led to cellular and molecular studies that have implicated myocilin to biological changes in intracellular, extracellular matrix, and cell-extracellular matrix functions. In a preliminary study, Borras et al. (353) hypothesize that the different biological effects associated with myocilin may act through second messenger effectors, which may change the gene expression profile within trabecular meshwork cells. They found that over expression of myocilin (delivered by adenovirus) in one human trabecular meshwork cell line altered gene expression in 10.6% of the transcripts when compared to the same cell line transformed with adenovirus alone (control). The authors speculate that gene expression changes in molecules such as angiopoietin-2, matrix metalloproteinase-1 (MMP-1), thrombomodulin, growth arrest specific-1, vascular cell adhesion molecule-1, and several molecules involved in the ubiquitination pathway may be mediators or effectors of the biological response to over expression of myocilin.
Although it is not surprising that cells transformed with replication-deficient adenovirus can alter gene expression in the host cells (Stilwell and Samulski, 2004), it is interesting to identify the genes whose mRNA levels were altered by over expression of myocilin. Performing microarray studies like the one presented by Borras et al. provide the opportunity to identify new candidate molecules that may have a functional association (direct or indirect) with myocilin. This may help establish a better understanding of the function normal myocilin has in trabecular meshwork cells.
Are the findings from cells from a single donor (the single cell line used in this study) representative of other donors? This is yet to be established. Comparisons of gene expression profiles from one cell line to another often vary. Genes that are found to be altered in all cell lines become the key molecules of interest. As the authors state, cell lines from several additional donors will need to be tested before generalizations can be made about the identity of the true mediators/effectors of the trabecular cell response due to over expression of myocilin.
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