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Editors Selection IGR 11-3

Basic research: Trabecular meshwork: Extracellular matrix and outflow facility

Comment by Ted Acott on:

17971 Effect of excess synthesis of extracellular matrix components by trabecular meshwork cells: possible consequence on aqueous outflow, Tane N; Dhar S et al., Experimental Eye Research, 2007; 84: 832-842

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In the interesting study by Tane et al. (420) it is shown that treatment of bovine and human trabecular meshwork ™ cells with high glucose or dexamethasone is to increase expression of two important basement membrane extracellular matrix (ECM) proteins, laminin and type IV collagen. Transfection of these cells with anti-sense oligonucleotides to these genes partially blocks the increased expression. These increases in laminin and type IV collagen expression are associated with decreases in small molecule permeability and electrical conductivity across confluent monolayers of cultured TM cells. The antisense oligonucleotides block these permeability and conductivity changes, establishing causality. This is a carefully controlled study and the observations are credible. The authors interpret these observations as support for the idea that increased ECM levels are related to increased aqueous humor outflow resistance. The interpretation is the weakest part of the paper. It is unclear how small molecule permeability or transelectrical conductivity would have any relationship to the aqueous humor outflow resistance. In addition, the outflow resistance is thought to reside within the juxtacanalicular and/or Schlemm's canal inner wall region of the outflow pathway. There are no continuous layers of TM cell in that region and Schlemm's inner wall cells normally behave very differently from TM cells. They are also backwards,i.e., basal to apical, relative to flow in the system. That increased laminin and type IV collagen can decrease monolayer permeability and conductivity is a littlesurprising and intriguing. Understanding the mechanism of this effect might be of interest. The ECM component change might also relate, albeit indirectly, to some important characteristics of the outflow pathway.

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