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Editors Selection IGR 10-4
Basic Science: Effects of Steroids on the Trabeculum
Comment by Abbot Clark on:
61276 Dexamethasone Stiffens Trabecular Meshwork, Trabecular Meshwork Cells, and Matrix, Raghunathan VK; Morgan JT; Park SA et al., Investigative Ophthalmology and Visual Science, 2015; 56: 4447-4459
Glucocorticoid (GC)-induced ocular hypertension (OHT) is an important side effect of prolonged GC treatment, which can lead to iatrogenic open-angle glaucoma that clinically is very similar to primary open-angle glaucoma. GCs induce a wide variety of changes in the trabecular meshwork (TM), but the molecular mechanisms responsible for GC-OHT are still unknown. A recent report by Raghunathan and colleagues has nicely shown that treatment with the potent GC dexamethasone stiffens TM cells and tissues, which they suggest contributes to GC-OHT. Treatment of cultured human TM cells with dexamethasone caused a significant increase in TM cell stiffness measured by atomic force microscopy (AFM). The authors removed the TM cells and used AFM to demonstrate that the extracellular matrix (ECM) of dexamethasone treated TM cells was also significantly stiffer compared to the ECM of control TM cells. Proteomic examination of this ECM showed increased expression of glaucoma-associated proteins including myocilin, decorin, fibrillin, and secreted frizzled related protein (SFRP1). SFRP1 is an antagonist of the Wnt signaling pathway, and previous studies have reported elevated SFRP1 in glaucomatous TM cells and tissues. Increased SFRP1 expression elevated IOP in perfusion cultured anterior segments as well as in mouse eyes. This suggests that there may be cross-talk between the GC and Wnt signaling pathways in the TM. Raghunathan and colleagues also treated rabbits with topical ocular 0.1% dexamethasone eye drops for three weeks, and showed that the dexamethasone treated TM tissues were also significantly stiffer compared to the TM of untreated eyes. The authors conclude that the GC mediated changes in biophysical properties of TM cells, tissues, and ECM (i.e., increased stiffness) are associated with increased aqueous outflow resistance and elevated IOP. Although these are important and significant findings, there is no direct evidence that these changes are responsible for GC-mediated changes in aqueous outflow resistance and elevated IOP. The rabbits in this study did not develop elevated IOP, and the GC responder status of the human TM cells used in these studies likely was unknown.
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