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Editors Selection IGR 8-4
Basic research: Steroids and TM
Comment by Abbot Clark on:
21002 Gene expression profiles of human trabecular meshwork cells induced by triamcinolone and dexamethasone, Fan BJ; Wang DY; Tham CC et al., Investigative Ophthalmology and Visual Science, 2008; 49: 1886-1897
Ocular hypertension is a serious side effect of glucocorticoid therapy, and this condition is becoming more common with increased intravitreal administration of potent glucocorticoids. Steroid-induced ocular hypertension is due to increased aqueous outflow resistance and is associated with a number of biochemical and morphological changes in the trabecular meshwork (TM). Fan et al. (508) recently studied the effects of 2 commonly used ophthalmic glucocorticoids, triamcinolone acetonide (TA) and dexamethasone (DEX), on TM gene expression. The authors report that both TA and DEX alter TM cell gene expression, and the gene expression profiles for each steroid are quite different from one another, although there is some overlap including the induction of MYOC. The authors state that a number of genes they identified as differentially expressed are located with known POAG loci and should be considered as glaucoma candidate genes. There are several issues that readers need to consider when trying to interpret the data from this study. The differences in gene expression between the DEX and TA treatments should not be surprising. The data reported for the TA treatment were after 12 hours of TA exposure, while DEX treatment was for seven days. In addition, the TA doses used were 0.1 and 1.0 mg/ml, corresponding to 0.23 and 2.3 mM of TA, while the DEX concentration was a more reasonable 100 nM. TA is not very soluble, so the vast majority of the TA in the culture medium probably existed as drug crystals. It is quite possible that these crystals settling onto the TM cell monolayers also altered gene expression, independent of the glucocorticoid effects. Almost all the data were derived from a single human TM cell line. Although the authors report statistically significant differences in gene expression, there were no biological replicates. There have been several other studies reporting the effects of DEX on TM gene expression, but comparison of the data from all these studies is complicated because of the different times of treatment, different gene expression platforms used, and differences in degree of TM cell confluency, among others. Additional studies of the effects of glucocorticoids on the TM are warranted because of the clinical, cellular, and biochemical similarities between steroid glaucoma and POAG.
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