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Editors Selection IGR 10-4

Genetics - TM

Comment by Abbot Clark on:

14761 Genome-wide expression profile of human trabecular meshwork cultured cells, nonglaucomatous and primary open angle glaucoma tissue, Liton PB; Luna C; Challa P et al., Molecular Vision, 2006; 12: 774-790

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Increased aqueous humor outflow resistance resulting in elevated IOP is a major causative risk factor for the development and progression of POAG. However, very little is currently understood about the molecular mechanisms responsible for this increased outflow resistance. Liton et al. (997)used gene chip arrays to profile and compare gene expression in cultured human trabecular meshwork (TM) cells and in TM tissues derived from normal (N) and POAG (G) donor eyes. They verified differential gene expression of a subset of genes using RT-QPCR. The gene expression profiles between TM cells and TM tissues were very similar (for > 90% of the expressed genes). However, there were important differences, such as decreased expression of MYOC, which has been reported previously, and increased expression of many extracellular matrix genes in the cultured TM cells. The authors identified ~ 150 genes with a 2-fold or greater differential expression between NTM and GTM tissue. This is the first published report of genome-wide differential gene expression between normal and glaucomatous TM tissue. They found increased expression of selectin E (also known as ELAM1) in glaucomatous TM tissue, which independently confirms an earlier report.¹ Cochlin mRNA was present in both NTM and GTM tissues, but there were no differences in expression levels. Cochlin protein levels had been previously reported to be elevated in glaucomatous TM tissues²). Decreased expression of ceruloplasmin and peroxonase may predispose GTM tissue to greater oxidative damage. In addition, the authors identified > 900 genes expressed in the TM that also map to 11 glaucoma loci, providing a list of potential glaucoma candidate genes for further analysis.

The authors have made all their gene expression data publicly available (in the GEO database) for others to use, but there are two important issues to consider with these data. POAG is a multifactorial and multigenic disease, and the Liton data represent the analysis of only 3 normal and 2 glaucomatous TM tissues. Another important difference between the sample sets (besides disease status) is the potential effect of glaucoma medications on gene expression. Despite these cautions, the authors have made an important contribution and valuable first step in identifying potential new pathogenic pathways and candidate glaucoma genes.

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