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Editors Selection IGR 8-2

Basic Science: Trabecular meshwork and aqueous homeostasis

Comment by Ernst Tamm on:

50936 Connective tissue growth factor-mediated upregulation of neuromedin U expression in trabecular meshwork cells and its role in homeostasis of aqueous humor outflow, Iyer P; Maddala R; Pattabiraman PP et al., Investigative Ophthalmology and Visual Science, 2012; 53: 4952-4962

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Connective tissue growth factor (CTGF) is a signaling molecule with high constitutive expression in the human trabecular meshwork TM. CTGF is induced by TGF-β2, and most if not all effects of TGF-β2 on TM extracellular matrix (ECM) synthesis are mediated through the action of CTGF. Moreover, CTGF has been shown to induce a contractile myofibroblast-like phenotype in TM cells. The actions of CTGF very likely induce higher resistance to aqueous humor outflow in the TM outflow pathways, since CTGF overexpression in the mouse eye leads to high intraocular pressure (IOP) and primary open-angle glaucoma (POAG). A similar mechanism might well account for the well-documented changes in TM outflow resistance in human POAG, as most affected patients show higher amounts of active TGF-β2 in their aqueous humor. Iver and co-workers have now revisited the action of CTGF on TM cells and nicely confirm previous studies and the tremendous effect of CTGF on the TM actin cytoskeleton and ECM synthesis. In addition, they provide evidence that CTGF is regulated closely by Rho GTPase, an effect that has previously only been shown in fibroblasts. The authors have now identified that neuromedin is induced in the TM in response to CTGF. Neuromedin is a neuropeptide that the authors show to partially mimic the effects of CTGF on the TM actin cytoskeleton. In summary this study nicely contributes to our understanding of the signaling factors that modulate TM ECM synthesis and contractility. Iver and colleagues confirm the important role that CTGF appears to play in the structural and functional changes of the TM during POAG. The modulation of this signaling pathway appears to be a very promising strategy for a causal treatment of the TM changes and their influence on IOP in POAG.

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