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Editors Selection IGR 12-2

Basic Research - Outflow: Aqueous outflow resistance

Comment by Terete Borras on:

46439 Segmental versican expression in the trabecular meshwork and involvement in outflow facility, Keller KE; Bradley JM; Vranka JA et al., Investigative Ophthalmology and Visual Science, 2011; 52: 5049-5057

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The paper by Keller et al. (1160) studying versican separately on segments of high and low trabecular meshwork (TM) flow opens a new avenue in the search for gene / protein involvement in outflow facility. The authors used labeled, HIV-TAT Qdots nanoparticles in perfused anterior segments to identify and isolate TM segments of higher and lower outflow (dense and sparse labeled regions). Because the TM segmental outflow is a reflection of the segmental resistance, tightly linked to extracellular matrix (ECM) composition, this system is ideal to study the role of versican, a chondroitin sulfate proteoglycan with a long TM-ECM history. The findings are complex but very interesting. Versican is more abundant in sparsely labeled TM segments (regions of higher resistance) than in densely labeled ones (easier flow). Versican isoforms in the higher resistance segments (sparse labeling) have more glycosaminoglycan (GAGs) side attachments, which in turn would result in more GAGs to alter ECM proteins interactions.

Versican is a significant player in outflow facility control

How these findings correlate with the downregulation of versican by stretch and elevated IOP is not clear. Versican also seems to have a fibrillar pattern perpendicular to the Schlemm's canal which the authors interpret as potential channels for fluid flow. These channels disappear when silencing versican in perfused cultures with shRNA lentiviruses. And, to add to the complexity, silencing versican increases outflow facility in human tissues but decreases it in pig, while silencing GAGs' biosynthesis increases outflow facility in both species. What emerges from all these results is that, although some clarifications are needed, versican is a significant player in outflow facility control. In addition, the paper has broader implications. Not only offers a more rigorous method to study outflow facility, but it calls for a re-evaluation of earlier TM immunohistochemistry work, where interpretations/comparisons were based in a few tissue sections without the awareness of segmental origin.

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